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Kacper Witek, Karolina Wydra, Agata Suder and Małgorzata Filip
Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland
Abstract: Recent preclinical studies report that the maternal fructose diet is a sufficient factor for changes in the emotional status of offspring. As well, individual mental health predispositions such as anxiety and depression have been identified as triggers to cocaine use disorder. Our preclinical study aimed to examine the impact of maternal fructose diet consumption on cocaine-seeking behavior in male offspring Wistar rats. Rats after maternal fructose diet during pregnancy and lactation were used in the intravenous cocaine self-administration (SA) models in an increasing fixed ratio (from FR1 to FR5) reinforcement schedule with a stable dose of cocaine (0.5 mg/kg/infusion) or increasing doses of cocaine (from 0.25 to 1 mg/kg/infusion) under a stable FR1. Later, we evaluated the rat's motivation in a progressive ratio test, abstinence in extinction training, and reinstatement of cocaine-seeking induced by conditional or unconditional stimuli. Our results showed that perinatal offspring exposure to fructose changed neither cocaine reinforcement nor cocaine motivation. Finally, we showed that fructose males displayed higher cocaine-induced reinstatement, suggesting that perinatal diet can change offspring sensitivity to the addictive psychostimulant.
Funding: This study was supported by the Department of Drug Addiction Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences statutory funds.
Zuzanna Sulich, Jakub Bilnicki, Aleksandra Kaczmarska, Wojciech Solecki
Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, Cracow, Poland
Abstract: Opiod withdrawal during abstinence in opioid-dependent patients is considered one of the major reasons for relapse to opioid-seeking and opioid-taking behaviors. This symptom of opoid use disorder (OUD) is associated with dysphoria and manifests in form of specific motivational/affective signs which can be modeled in animal models of OUD. Here we aimed to demonstrate behavioral responses accompanying oxycodone withdrawal. We used male Sprague-Dawley rats and acute and chronic oxycodone administration to induce opioid physical dependence. To induce opioid withdrawal animals were pretreated with naloxone (1 mg/kg) 3h prior to last oxycodone administration. We used saline treated rats as controls. We used conditioned place aversion as well as measurement of ultra-sonic vocalizations (USV) to measure motivational/affective symptoms of withdrawal. Naloxone administration induced significant place aversion in both acute and chronic oxycodone- (but not saline) treated rats. In addition, several somatic signs of withdrawal were present after naloxone administration. Interestingly, naloxone-induced oxycodone withdrawal was not accompanied by increased aversive/dysphoric (22 kHz) USV. Together, our results demonstrate that naloxone-precipitated oxycodone withdrawal in rats is associated with robust dysphoria which can be readily measured in conditioned place aversion paradigm.
Funding: National Science Centre grants no: UMO-2020/39/B/NZ7/03537
Maurilio Menduni De Rossi1,2; Olivia Stupart3; Jeffrey Dalley3
1Institute of Life Sciences, Sant’Anna School of Advanced Studies, Pisa, Italy;
2Faculty of Medicine and Surgery, University of Pisa, Pisa, Italy;
3Department of Psychology, University of Cambridge, Cambridge, United Kingdom
Abstract: Neglect, the failure to provide children with physical and emotional needs is known to alter the development of biological stress response systems. The current study examined the neurobehavioural consequences of maternal separation (MS) in rats, a procedure mimicking the environmental conditions of neglect, and investigated whether this paradigm altered the response to acute treatment with stress-related drugs later in life. 64 adult rats (equally divided for group and sex) were assessed for behavioural flexibility and feedback sensitivity, measures linked to psychiatric vulnerability in humans, on a spatial probabilistic reversal learning task. We did not find evidence of cognitive deficits in MS rats, instead only female MS rats had a better task performance than controls and this difference was also present after the acute administration of corticosterone, an unpredictable stressor. Propanolol administration, used to treat task-based anxiety, had positive or negative effects on the key measure for cognitive flexibility in control females and MS rats respectively. Citalopram, a common antidepressant, had the opposite effect, increasing cognitive flexibility only in MS female rats and decreasing task performance in control females. Our results suggest a putative resilient phenotype in MS females that confers them better task performance and better response to unpredictable stress later in life but affects their treatment outcomes differently. Indeed, we bring evidence to suggest that in rats the effects of acute administration of propranolol and citalopram are consistently present only in females and gain different outcomes for control and MS rats. Our findings may have translational relevance to test for personalised care based on sex and maltreated status that could lead to better treatment outcomes.
Funding: Support provided by the Amgen Foundation
Julia Netczuk1, Klaudia Misiołek1, Łukasz Szumiec1, Krystyna Gołembiowska2, Jan Rodriguez Parkitna1
1Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences
2Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences
Abstract: κ-Opioid receptors (KORs) play a major role in the regulation of the activity of the brain’s serotonergic system and accordingly have long been investigated as a potential target for the treatment of anxiety or affective disorders. Here we assessed the behavioural phenotype of female and male mice with selective inactivation of KORs on serotonergic (5-HT) neurons (Oprk1Tph2CreERT2 strain). Initial behavioural characterisation revealed no apparent mutation effects, normal activity in the open field, and an intact preference for sweet taste. Thus, we performed the light-dark box test to measure an unconditioned anxiety response. We observed a significant effect of interaction between sex and genotype on latency to enter the light box. Next, we analysed the contents of monoamines in the striatum (STR) and frontal cortex (FC). Considering the 5-HT neuron function, we found a significant effect of sex on 5-HT levels in FC and an interaction between sex and genotype. There was a significant effect of genotype on noradrenaline level in STR and dopamine (DA) level in FC. In terms of sex differences, we observed a significant effect of sex on DA levels (PFC and STR), 5-hydroxyindoleacetic acid (PFC and STR), homovanillic acid (STR), and 3-methoxytyramine (STR). Thus, we find that the loss of KORs on serotonergic neurons causes a sex-dependent change in anxiety-like behaviours.
Funding: National Science Centre, Poland OPUS 2019/35/B/NZ7/03477.
Justyna Grymuza, Barbara Budzyńska
Independent Laboratory of Behavioral Studies, Medical University of Lublin, Lublin, Poland
Abstract: Nowadays globally, there is an ongoing rise of neurological disorders such as Alzheimer disease, which is the leading cause of dementia. Currently, no effective treatment for dementia is known. Therefore, the development of new animal models to evaluate the procognitive effects of new molecules is needed.
Zebrafish exhibit anatomical similarities to the mammalian brain, characterized by high homogeneity of hippocampus-like and amygdala-like structures, the primary areas responsible for memory in the human brain. Moreover, zebrafish demonstrate a resemblance in cholinergic, glutamatergic, and monoaminergic signaling, making them an appropriate neurobiological model for designated research.
The study aimed to establish a novel model of memory impairments in adult Danio rerio induced by scopolamine (50, 100, 150 μM), a cholinolytic agent. Spatial memory and response to novelty in zebrafish were assessed using the Y maze. Study results showed that scopolamine impairs memory processes in zebrafish. These effects were sex-dependent as scopolamine decreased the time spent in the novel arm in males solely in the highest concentration and in females both at 100 μM and 150 μM concentrations.
In conclusion, this study provides evidence that the proposed zebrafish behavioral model may be considered an effective platform for developing therapies for neurological disorders.
Julia Brodowska1, Jana Svobodova Burianova2, Jiri Ruzicka1, Jan Svoboda3,4, Pavla Jendelova1, James W Fawcett2,5 and Jessica CF Kwok1,6
1Departament of Neuroregeneration, Institute of Experimental Medicine, CAS, Prague, Czech Republic.
2Reconstructive Neuroscience Research Centre, Institute of Experimental Medicine, CAS, Prague, Czech Republic.
3Laboratory of Neurophysiology of Memory, Institute of Physiology, CAS, Czech Republic.
4Faculty of Science, Charles University, Prague.
5John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
6Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Abstract: Perineuronal nets (PNNs) enwrap selected populations of neurons and are involved in the regulation of neuroplasticity. Their composition shifts during the critical period (CP) of brain development and continues to change through ageing, correlating with cognitive decline. Chondroitin sulfates are key components of PNNs, and the ratio of their sulfation patterns changes in favour of C4S over C6S upon maturation, leading to increased inhibitory properties of PNNs. In the current study, we are exploring the function of C4S in cognition, using chondroitin 4-sulfotransferase (Chst11) KOs under parvalbumin (PV) promoter in contrast with WT animals of 3 and 6 months of age. To evaluate short-term memory, we performed Novel Object Recognition (NOR) and Morris Water Maze (MWM) tasks; sociability was evaluated through the Three Chamber Task (TCT). Chst11 KO mice have shown generally improved short-term memory compared to WT mice. Results from TCT suggest that KOs' general sociability is preserved. In conclusion, Chst11 KOs showed consistent cognitive superiority over wild types and had no decrement in sociability, suggesting C4S’s to be a promising target for therapies for disorders causing cognitive decline, such as in Alzheimer’s disease.
Funding: Grant No: GAČR 23-05540S.
Alicja Radzimska1, Anna Janus1, Henryk Marona2, Klaudia Lustyk1, Karolina Pytka1
1Department of Pharmacodynamics, Faculty of Pharmacy Jagiellonian University Medical College, Cracow, Poland
2Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland
Abstract: Cognitive deficits, prevalent in affective disorders, significantly decrease the quality of patients’ lives. Moreover, the majority of antidepressants fail to address memory impairments associated with depression. Therefore, as a continuation of the study on HBK-14, a dual 5-HT1A and 5-HT7 antagonist with proven antidepressant-like and anxiolytic-like activity in rodents, we now aim to evaluate its potential to mitigate memory impairments. We used a passive avoidance test to examine HBK-14’s effects on long-term emotional memory in male mice. Memory deficits were induced by the administration of an NMDA receptor antagonist, MK-801, or a muscarinic receptor antagonist, scopolamine. HBK-14 was tested at doses of 0.625, 1.25, and 2.5 mg/kg, with rivastigmine employed as a reference drug. At a dose of 2.5 mg/kg, HBK-14 significantly increased latency to enter the dark chamber in the retention trial compared to the MK-801-treated control group. However, it did not protect animals from memory impairments induced by scopolamine. In summary, our study indicates that HBK-14 has the potential to mitigate long-term emotional memory deficits associated with glutamatergic system imbalance. This encourages further research to explore mechanisms underlying HBK-14's antiamnestic effect.
Natalia Płachtij1, Aleksandra Manik1, Karolina Kania1, Filip Targosiński1, Stanislav Gobec2 and Kinga Sałat1
1Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
Abstract: Introduction: Available drugs for Alzheimer’s disease (AD) attenuate memory loss only in the mild to moderate phase of the disease. Therefore, novel procognitive drugs candidates are urgently needed.
Two enzymes: butyrylcholinesterase (BuChE) and p38α mitogen-activated protein kinase (p38α MAPK) are involved in neurodegeneration in the course of AD, so they seem to be potential therapeutic targets for anti-AD drugs. This study investigated procognitive properties of compounds GUK-1329 (a selective BuChE inhibitor), KES-19 (a selective p38α MAPK inhibitor) and KES-29 (a dually-acting BuChE/p38α MAPK inhibitor) in mouse models of amnesia induced by scopolamine or lipopolysaccharide.
Methods: Passive avoidance (PA), novel object recognition (NOR) and Morris water maze (MWM) tasks were used to assess the activity of compounds administered intraperitoneally.
Results: In the scopolamine model KES-29 was the most active compound in the PA and NOR tasks. In the lipopolysaccharide model KES-29 was the most effective compound which improved spatial learning and memory measured in the MWM task. None of the test compounds induced motor deficits in mice.
Conclusions: Since KES-29 was the most effective antiamnesic agent, it can be concluded that combining two mechanisms in one molecule (multi-target-directed ligands) is a promising approach to develop effective anti- AD drug candidates.
Funding: Financial support from the National Science Centre (grant No. DEC-2021/43/I/NZ7/00342) is gratefully acknowledged.
Elżbieta Żmudzka1, Klaudia Lustyk2, Kinga Sałaciak2, Małgorzata Wolak3, Jolanta Jaśkowska4, Jacek Sapa2, Karolina Pytka2
1Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
2Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
3Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
4Department of Organic Chemistry and Technology, Faculty of Chemical and Engineering and Technology, Cracow University of Technology, Krakow, Poland
Abstract: In view of the ageing population, the prevalence of dementia or Alzheimer disease is expected to be rising. Progressive loss of memory, cognitive deficits and behavior impairments affect patient’s daily functioning and quality of life. Unfortunately, there are limited therapies available, which also aren’t effective enough. For that reason, the investigation for novel potential anti-amnesic drugs still remains one of the major challenge for neuroscientists. The aim of this study was to explore the novel compound SD1, which is a salicylamide derivative, and test its influence on the long-term emotional and recognition memory in mice. First, we performed passive avoidance task, where the latency to enter the dark compartment was measured. Then, we conducted object recognition test and we measured the time of novel object exploration by mice. Finally, we evaluated, if the compound may ameliorate memory deficits induced by MK-801. All tests were performed using male CD1 mice. The tested compound significantly increased the latency time in the passive avoidance task at the doses 0.625-2.5 mg/kg, whereas it reversed MK-801-induced cognitive disturbances only at one dose (1.25 mg/kg) during this test. On the other hand, the compound did not increase the time of novel object exploration in the object recognition test. Results of this study suggest that novel compound SD1 might improve long-term emotional, but no recognition, memory impairments in rodents and it could be a promising structure in developing novel anti-amnesic agents.
Kinga Sałaciak1, Monika Głuch-Lutwin2, Barbara Mordyl2, Klaudia Lustyk1, Karolina Pytka1
1Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland
2Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Krakow, Poland
Abstract: Biased agonists exhibit a preference for activating specific signalling pathways, offering potential for innovative treatment strategies that demonstrate pharmacological activity without inducing undesired effects. Our investigation, building on previous research confirming the rapid antidepressant-like properties of a 2-methoxyphenylpiperazine derivative named HBK-15 in rodents, focuses on exploring its memory-enhancing activity and potential functional selectivity upon selected serotonin and dopamine receptors. Employing various cell-based functional assays, we assessed the intrinsic activity of HBK-15 at 5-HT1A, D2S, D2L, and D4 receptors, examining its effect on cAMP production, ß-arrestin recruitment, and/or phosphorylation of ERK1/2. To evaluate the potential antiamnesic properties of HBK-15, we induced memory deficits in mice using NMDA receptor antagonist MK-801, followed by Morris water maze test to assess long-term spatial memory. Our findings revealed varying efficacy and potency of HBK-15 across different signalling pathways, showcasing its functional selectivity at the 5-HT1A, D2S, D2L, and D4 receptors. Furthermore, HBK-15 effectively reversed spatial memory impairments induced by the glutamatergic imbalance. Collectively, these results underscore HBK-15 as a promising candidate for mitigating memory impairments through a distinctive mechanism of action.
Funding: This study was conducted as part of a research project funded by the National Science Centre, Poland (grant 2019/34/E/NZ7/00454).
Filip Kosior1, Henryk Marona2, Klaudia Lustyk1, Karolina Pytka1
1Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland
2Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland
Abstract: Cognitive deficits in neuropsychiatric disorders, such as depression and anxiety, necessitate novel therapeutic approaches. HBK-14, a dual 5-HT1A and 5-HT7 receptor antagonist, has shown promise in preclinical studies for its antidepressant-like properties. Expanding upon the previous study on HBK-14, we now aim to investigate its antiamnesic properties using the object recognition test in mice.
Male CD-1 mice underwent the object recognition test with a time interval of 24-h between the familiarization and test sessions. HBK-14 was tested at doses of 0.625, 1.25, and 2.5 mg/kg. We used scopolamine, a muscarinic receptor antagonist, to induce memory impairments, and rivastigmine as a reference compound.
We found that scopolamine at a dose of 1 mg/kg induced long-term recognition memory impairment. HBK-14 at a dose of 2.5 mg/kg showed a tendency to protect animals from cognitive deficits, however, the effect was not statistically significant.
Further research is needed to explore the pharmacological potential of HBK-14.
Kristýna Mazochová1, Klára Šíchová1, Vladimír Mazoch1, Hynek Danda1,2, Tomáš Páleníček1,2
1Psychedelic Research Center, National Institute of Mental Health, Klecany, Czech Republic
23rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
Abstract: Methoxphenidine (MXP) is a synthetic dissociative substance that has gained attention as a designer drug. MXP belongs to the diarylethylamine class and shares structural features with arylcyclohexylamines, such as phencyclidine, ketamine, and methoxketamine.
Despite the potential harmful effects of MXP, our knowledge and understanding of the influence of this new synthetic substance on living organism remained limited hence our primary target was to enrich current knowledge of MXP.
Our main intention was to describe in detail the effects of MXP (10, 20, and 40 mg/kg subcutaneously, s.c.) in two behavioral behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field and sensorimotor gating in the test of prepulse inhibition (PPI). To correlate the behavioral data with serum levels of MXP, the samples for pharmacokinetics were measured using liquid chromatography mass spectrometry.
10 and 20mg/kg MXP induced significant locomotor stimulation, whereas 40mg/kg reduced locomotion and increased time spent in the centre of the arena, suggesting sedation/anaesthesia or stereotypy. The duration of the effects was present for at least 60-90min. MXP decreased baseline acoustic startle response (ASR) and disrupted PPI, irrespective of testing onset. Maximal brain levels of MXP were observed 30min after administration, remained high at 60min and progressively declined to around zero after 24 hours.
Our findings indicate that MXP behaves as a typical dissociative anaesthetic with stimulant effects at lower doses, sedative/anaesthetic effects at higher doses, and as a disruptor of sensorimotor gating. MXP was found to be a mild stimulant, with anxiogenic and psychomimetic properties, which indicates that in acute human intoxication, unpleasant experiences and potentially negative psychological sequelae might result.
Funding: This work was supported by grant from Czech Health Research Council (project NU21-04-00307), Czech Science Foundation (projects 20-25349S and 21-32608S), Ministry of the interior of the Czech Republic (project VK01010212), Long-term conceptual development of research organization (RVO 00023752), and Specific University Research, Czech Ministry of Education, Youth and Sports (project 260648/SVV/2024), ERDF-Project Brain dynamics, No. CZ.02.01.01/00/22_008/0004643, project VVI CZECRIN (LM2023049) and Charles University research program Cooperatio-Neurosciences and private funds obtained via PSYRES, Psychedelic Research Foundation (https://psyresfoundation.eu).
Klára Šíchová1, Barbara Mallarino1, Kristýna Mazochová1, Lucie Ladislavová1, Lucie Janečková3, Čestmír Vejmola1,2, Tomáš Páleníček11,2
1Psychedelic Research Center, National Institute of Mental Health, Klecany, Czech Republic
23rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
3Forensic Laboratory of Biologically Active Compounds, Department of Chemistry of Natural Compounds, Czech Republic
Abstract: Hexahydrocannabinol (HHC) is a semi-synthetic cannabinoid that has attracted interest due to its potential psychotropic effects similar to those of natural cannabinoids. This substance is frequently abused in several EU and US countries where it serves as a legal and readily available alternative to ∆9-tetrahydrocannabinol (∆9-THC). Despite its widespread use, only a limited number of studies have addressed its effects and safety profile. In this study, we investigated the pharmacokinetics, systemic toxicity and acute behavioural effects following oral administration of HHC to male Wistar rats. Two hours after administration of 10 mg/kg, HHC concentrations peaked in both blood serum and brain tissue. According to the OECD Toxicity Assay 423, HHC was classified as a Category 4 substance with a lethal dose of 2000 mg/kg. Behavioural effects were evaluated using the Open Field and Prepulse Inhibition of Acoustic Startle Response tests, with three different doses (1, 5, and 10 mg/kg) co-administered with sunflower oil (placebo). Compared to placebo, the higher dose (10 mg/kg) induced reduced locomotor activity, increased anxiety and impaired sensorimotor gating. In summary, HHC readily crosses the blood-brain barrier, exhibits mild toxicity and produces behavioural effects similar to other cannabinoids.
Funding: This work was supported by a grant from Czech Health Research Council (project NU21-04-00307), Czech Science Foundation (23-07578K), Ministry of the Interior of the Czech Republic (project VK01010212), Long-term conceptual development of research organization (RVO 00023752), and Specific University Research, Czech Ministry of Education, Youth and Sports (project 260648/SVV/2024), ERDF-Project Brain dynamics, No. CZ.02.01.01/00/22_008/0004643, project VVI CZECRIN (LM2023049) and Charles University research program Cooperatio-Neurosciences and private funds obtained via PSYRES, Psychedelic Research Foundation (https://psyresfoundation.eu).
Zuzanna Kościuk, Agnieszka Bysiek, Izabela Szpręgiel, Krystyna Gołembiowska
Department of Pharmacology, Unit II, Maj Institute of Pharmacology, Polish Academy of Sciences, Cracow
Abstract: Classic psychedelics (psychoplastogens) show their main mechanism of action through 5-HT2A receptors. These receptors are located on layer V pyramidal neurons and GABA-ergic interneurons of the prefrontal cortex. It appears that the highest density of 5-HT2A receptors is found in the subcortical structure, the claustrum, which has both afferent and efferent connections to virtually all areas of the cortex. However, there is currently a paucity of information regarding the effects of psychedelics on 5-HT2A receptors in the claustrum and the transmitters that are released into the synaptic space as a result of their activation.
This study examined the effect of activation of 5-HT2A receptors in the claustrum on the levels of neurotransmitters released. The compound 25I-NBOMe, which is their high-potency agonist, was used to activate 5-HT2A receptors. This effect was studied in freely moving rats, and 25I-NBOMe was administered through a microdialysis probe to the claustrum at the concentration of 500 μM. The results examined by chromatographic techniques showed an increase in the release of monoamines (serotonin, dopamine, and norepinephrine) and glutamate, while a decrease in inhibitory GABA-ergic transmission was observed. The obtained data will allow us to understand better the mechanism of action of psychedelic substances.
Funding: This research was funded by National Science Centre grant no. 2020/37/B/NZ7/03753 and statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences.
Isis Koutrouli1,2, Hynek Danda1,2, Kristýna Štefková-Mazochová1, Nikola Pinterová-Leca1,2, Vladimír Mazoch1, Tomáš Páleníček1,2
1Department of Experimental Neurobiology, National Institute of Mental Health, Klecany, Czech Republic
23rd Faculty of Medicine, Charles University, Prague, Czech Republic
Abstract: Baeocystin (4-phosphoryloxy-N-methyltryptamine) is a naturally occurring indole (tryptamine) alkaloid, found in many Psilocybe species among other psychoactive mushrooms. Because of its structural similarity with psilocybin (and psilocin), and since the latter displays beneficial effects in the treatment of various psychiatric disorders, baeocystin has garnered interest regarding whether it shares such effects with psilocybin. Therefore, behavioral aspects of acute administration of baeocystin were investigated in this study, namely prepulse inhibition (PPI), as it reflects the sensorimotor disruption of information that psychedelic substances commonly display, and locomotor activity in the open field test (OFT), as a marker describing the degree of inhibition or activation. Wistar rats were administered with either 1,25 or 5 mg/kg subcutaneously. Analyses report that baeocystin has no potency to disrupt PPI; furthermore, no significant effects were observed in locomotor activity. Thus, our preliminary results suggest no psychedelic activity. Future investigation on the pharmacokinetic/pharmacodynamic characteristics of baeocystin will further delineate the profile of this yet unexplored substance.
Funding: This work was supported by a grant from Czech Health Research Council (project NU21-04-00307), Czech Science Foundation (23-07578K), Ministry of the Interior of the Czech Republic (project VK01010212), Long-term conceptual development of research organization (RVO 00023752), and Specific University Research, Czech Ministry of Education, Youth and Sports (project 260648/SVV/2024), ERDF-Project Brain dynamics, No. CZ.02.01.01/00/22_008/0004643, project VVI CZECRIN (LM2023049) and Charles University research program Cooperatio-Neurosciences and private funds obtained via PSYRES, Psychedelic Research Foundation (https://psyresfoundation.eu).
Mindaugas Potapovas1, Čestmír Vejmola2,3, Evaldas Pipinis1, Tomáš Páleníček2,3, Inga Griškova-Bulanova1,2
1Institute of Bioscience, Vilnius University, Vilnius, Lithuania
2National Institute of Mental Health, Psychedelic Research Center, Klecany, Czech Republic
3Charles University, Third Faculty of Medicine, Praha, Czech Republic
Abstract: Serotonergic psychedelics are gaining attention for treating neuropsychiatric disorders. Psilocybin mimics psychotic symptoms, serving as a model for serotoninergic psychosis. The 40 Hz auditory steady-state response (40 Hz ASSR) reflects gamma-range activity, showing decreased inter-trial phase coherence (ITPC) under psilocybin. However, animal data on serotonergic ASSR modulation are limited. Our study examines 40 Hz ASSR changes in rats given 1 mg/kg psilocin. Nine adult male Wistar rats were implanted with EEG electrodes to record neural activity. Auditory stimulation was used to elicit the 40 Hz responses. Results revealed significantly increased ITPC at the A4 electrode (right hemisphere) post-psilocin, compared to saline, with no significant change at A3 (left hemisphere). This suggests an asymmetric pattern of effects induced by psilocin. While functional asymmetry of the auditory cortex is known in rodents, the observed rise in ASSR ITPC values over the right hemisphere is unprecedented, differing from effects seen in humans or rodents previously. Findings highlight the need for further study on psilocin's impact on rodent ASSR generation mechanisms. Insight into these mechanisms could inform therapeutic applications of serotonergic psychedelics for neuropsychiatric disorders. Additionally, understanding differences in ASSR modulation between humans and rodents could enhance the translational validity of animal models.
Mateusz Królewski*, Magdalena Białoń*, Katarzyna Popiołek-Barczyk, Żaneta Michalec-Warzecha, Katarzyna Starowicz
*Equal contribution
Department of Neurochemistry, Maj Institute of Pharmacology, Cracow, Poland
Abstract: Background: Schizophrenia is severe mental illness that can be modeled in animals through the administration of NMDA receptor antagonists, e.g. MK-801, leading to alterations related to those observed in the disease. Endocannabinoid system (ECs) is strongly implicated in pathophysiology of neuropsychiatric disorders such as schizophrenia. β-caryophyllene (BCP), an agonist of CB2 receptor, exerts anti-inflammatory and anxiolytic activity, therefore we aimed to verify its effects on schizophrenia-related behaviors and dopamine (DA) frontal metabolism.
Methods: Male Wistar rats were injected once daily for 5 days with saline, vehicle, MK-801, BCP or BCP and MK-801 combined. Travelled distance, entries into the inner zone (IZ) and % time spent in the IZ were measured in the open field test to assess locomotor activity and anxiety behavior. DA and its metabolites levels in frontal cortex (FCX) were measured using high-performance liquid chromatography. One-way ANOVA and post hoc Tukey test were employed for statistical analysis.
Results: BCP ameliorated MK-801-induced hyperactivity, however, we observed no changes in anxiety-related behavior. BCP restored DA frontal metabolism to control level.
Conclusions: Positive effects of BCP on locomotor activity may be related to regulatory function of ECs on dopamine neurotransmission in FCX.
Funding: The study was financed from NSC Grant no.2022/45/N/NZ7/04059
Izabela Szpręgiel, Agnieszka Bysiek, Adam Wojtas, Krystyna Gołembiowska
Department of Pharmacology, Unit II, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Abstract: Clinical studies provide evidence that psilocybin could be used as fast-acting antidepressant but its mechanism of action on the HPA axis activity is still not fully understood.
The aim of the study was to determine the effect of a single psilocybin dose (0.6 mg/kg) on monoamine levels in the hypothalamus (HT) and adrenal glands (AD) of rats using HPLC. In addition, serum corticosterone (CRT) concentration was determined by ELISA method.
Psilocybin significantly increased the level of dopamine (DA) without affecting the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites DOPAC, HVA and 5HIAA as measured 7 days after administration. Any influence of psilocybin was observed on the tissue levels of NA, adrenaline (ADR), DA and 5-HT in the AD. Serum CRT concentration was decreased 7 days after psilocybin administration.
The obtained results indicate that psilocybin can modulate HPA axis function with possible involvement of hypothalamic DA pathways. The impact of psilocybin on HT-HPA may underlie the antidepressant effect of psychedelics.
Funding: National Science Centre grant no. 2020/37/B/NZ7/03753 and statutory funds of the Maj Institute of Pharmacology, Polish Academy of Sciences.
Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas, Krystyna Gołembiowska
Department of Pharmacology, Unit II, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Abstract: Mood and anxiety disorders are one of the most common threats to mental health, while expressing high levels of comorbidity. Psilocybin as selective agonist of 5-HT2A receptor seems to exhibit rapid antidepressant and anxiolytic effect in comparison to currently used antidepressant drugs.
The aim of this study was to measure the effect of acute low dose of psilocybin (0,6mg/kg) in frontal cortex on 35mM KCl-evoked neurotransmitters release in naive and chronic mild stressed rats. The levels of noradrenaline (NA), dopamine (DA), serotonin (5-HT), glutamate (GLU) and γ-aminobutyric acid (GABA) in the frontal cortex were measured by UHPLC using microdialysis in freely moving rats.
Except GABA, psilocybin increased evoked release of NA, DA, 5-HT and GLU in naive rats. In contrast, psilocybin decreased DA, 5-HT and GABA release but did not affect NA and GLU level in stressed animals. It may be concluded that increased release of neurotransmitters in naive rats seems to be mediated by 5-HT2A receptor that could be dysfunctional in stressed animals. The recruitment of 5-HT1A receptors under stressed conditions may be responsible for inhibitory psilocybin effect on DA, 5-HT and GABA release.
Funding: National Science Centre grant no. 2020/37/B/NZ7/03753 and Statutory funds of Department of Pharmacology, Unit II, Maj Institute of Pharmacology, Polish Academy of Sciences
Savani Anbalagan
Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poznań, Poland
Abstract: I recently proposed gasocrine signaling for gas-gasoreceptor protein interactions-driven cellular signaling (Anbalagan et al., 2024 Am J Physiol Endocrinol Metab.). To investigate gasocrine signaling, there is a critical need to identify gasoreceptors for the essential gasotransmitters like O2. Based on existing scientific literature, I propose that heme-based O2 sensors, featuring diverse signaling domains across genera, should be explicitly designated as O2 gasoreceptors. Acknowledging that O2 gasoreceptors are likely to belong to multiple protein classes with diverse signaling domains and pathways will facilitate a comprehensive search for O2 gasoreceptors in all organisms and across every cell type. This approach will broaden the investigation beyond specialized tissues or cells, encompassing a systemic exploration.
Pastukhov O.O.1, Pervak M.P.2, Smirnov I.V.3, Bukreeva N.I.5, Litvinenko M.V.4, Godlevsky L.S.1
1Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
2Simulative Medical Technologies Department, Odesa National Medical University, Odesa, Ukraine
3Ukrainian Research Institute of Medical Rehabilitation and Resort Therapy, Odesa, Ukraine
4Histology, cytology, embryology, and pathology department with the course of forensic medicine, Odesa National Medical University, Odesa, Ukraine
5Molecular and Genetic Laboratory, Odesa National Medical University, Odesa, Ukraine
Abstract: Manifestations of metabolic syndrome (MS) manifestations in chronic epilepsy models were in the scope of the investigation. Kindling was induced by daily injections of PTZ (Sigma-Aldrich) at a dose of 35.0 mg/kg i.p. for three weeks. Those animals with fully developed generalized seizures were used for investigations. Glucose and insulin levels were not different from control rats, while PTZ-kindled rats demonstrated decreased tolerance to glucose tests. Pentoxiphylline administration(100/0 mg/kg, i.p., during a week daily) caused partial restoration of glucose tolerance test and the inhibition of kindled seizures. On H&E stained liver of PTZ-kindled rats, the hepatocytes with normal vesicular nuclei were present with a deep acidophilic cytoplasm in some cells. The binucleated hepatocytes were scarcely present. The focal aggregation of mononuclear inflammatory cells between the hepatocytes with deep acidophilic cytoplasm and small, shrunken, deeply stained nuclei was seen. Also, the sparse presence of the hypertrophied intra-sinusoidal Von Kupffer cells between the hepatocytes was registered. In the PTZ-treated liver tissues, some central fatty deposits and additional smaller microdeposits around the hepatocytes with increased infiltration of Von Kupfer cells encroaching on those fatty lipid deposits were determined. The data favored moderate functional and morphological deteriorations in PTZ-kindled rats corresponding to metabolic syndrome.
Funding: This research was funded by the Ministry of Health Care of Ukraine (Number of research work 0121U114510).
Jakub Frydrych, Ewa Trojan, Krzysztof Łukowicz, Beata Grygier, Agnieszka Basta-Kaim
Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology PAS, Cracow, Poland
Abstract: Alzheimer's disease (AD) is a major public health concern, with observed changes in peripheral immune cell behavior potentially shedding light on brain dysfunction mechanisms. Studying primary and secondary immune cell populations may provide valuable insights into these processes.
This research aimed to study the cognitive changes and profile of immune cells in the brain and the periphery in the APPNL-F/NL-F mice model of AD (KI).
9-month-old C57BL/6J WT and KI mice were sacrificed, and their hippocampi and frontal cortices were dissected. Mouse ApoE, Aβ42/Aβ40 ratio, and cytokine levels (IL-1β, IL-6) were measured using ELISA test. Additionally, the proliferative response of splenocytes and metabolic activity of splenocytes and thymocytes (MTT, LDH, NO) after lipopolysacharide (LPS) and/or concanavalin A (ConA) stimulation were examined.
Despite intact spatial memory, KI mice showed elevated Aβ42/Aβ40 ratio, ApoE levels, and pro-inflammatory cytokines. Differential cellular reactivity was observed, particularly in the spleen, with increased LDH and NO release from KI mouse splenocytes upon ConA and LPS stimulation.
Thus, we demonstrated that brain immune status and peripheral immune cell reactivity are affected in AD and predict the occurrence of cognitive disturbances.
Funding: Funded by the National Science Centre, Grant No: 2021/43/B/NZ4/01133; Task number 7
R. Gmyrek1, N. Bylewska1, N. Konopińska1, J. Lubawy1, G. Nowicki2, K. Walkowiak-Nowicka1, A. Urbański1
1Department of Animal Physiology and Developmental Biology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
2genXone S.A., Złotniki, Poland
Abstract: Cooperation between the nervous and immune systems is one of the essential factors for maintaining homeostasis in animals. A crucial role in this process plays neuropeptides and their receptors. Our study aimed to analyse the dependence between the activation of the immune system and the allatotropin system, which has many functional similarities to the orexins system in vertebrates. Firstly, we identified the presence of transcripts of genes encoding allatotropin precursor and receptor in the nervous system (brain and ventral nerve cord) and immune-related cells (haemocytes and fat body). Secondly, to verify if allatotropin signalling takes part in the regulation of the immune system, we tested whether the application of immune activators affects the expression of genes encoding allatotropin precursor and receptor. The obtained results confirmed this supposition. However, the observed changes in the expression level of gene encoding allatotropin precursor and receptor depend on phase of infection, type of immune activator and tested cells. Additionally, we have shown that cytokines, also in insects, can modulate the neuropeptide signalling. All these results are important steps in understanding the evolutionary basis of hormonal regulation of the immune response.
Funding: This research was partially supported by a research grant from the Initiative of Excellence– Research University (102/13/SNP/0013).
N. Bylewska, R. Gmyrek, N. Konopińska, S. Tchórzewska, A. Urbański
Department of Animal Physiology and Developmental Biology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
Abstract: Despite wide knowledge about the activity of insect immune system, some aspects, such as the hormonal regulation of immune response require further studies. The results of current research suggest that the crucial compounds that link insect neuroendocrine and immune systems are neuropeptides, such as allatotropins (AT).
In the presented research, the influence of Tenmo-AT on immune system activity of mealworm beetle, Tenebrio molitor was analysed. For example, the injection of different concentrations of Tenmo-AT
(10-7 M and 10-5 M) increased the number of circulating haemocytes. Moreover, this neuropeptide also affects cellular and humoral mechanisms, such as phagocytic activity of haemocytes and enzymatic activity of haemolymph. Additionally, the injection of Tenmo-AT influences the expression levels of immune-related genes in the fat body and haemocytes of T. molitor. It should be noted that the most of the observed effects were time and dose dependent.
The obtained results allow to better understand the role of insect neuropeptides in the regulation
of the immune response. Due to partially structural and functional homology of insect AT and vertebrate orexins, our study is also an important step in research concerning the evolution of neuropeptide signalling.
Funding: This research was partially supported by a research grant from the Initiative of Excellence – Research University (102/13/SNP/0013).
Oliwia Jankowska1, Martyna Szozda1, Aleksandra Bochnak1, Karolina Warzecha1,
Joanna Jędrusik1,2, Milena Damulewicz1
1Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
Abstract: Parkinson's disease is a neurodegenerative disorder in which dopaminergic cells located in the brain undergo atrophy primarily causing movement disorders such as the characteristic tremor. Less well-known, but equally important symptoms involve digestive system dysfunction and disturbance of the diurnal clock rhythm. Our study attempts to link sleep deprivation with gut –brain axis dysfunction using Drosophila melanogaster model. This model was chosen due to the conservation of many genes, signalling processes, cellular mechanisms and neuronal processes. Organized central nervous system and well-described behavioural phenotypes along others are the reasons why Drosophila was already used in numerous studies of the circadian clock or neurodegenerative disorders. In our experiments young wildtype Canton S, white mutant and park mutant male flies were subjected to 17 hours of mechanical sleep deprivation. Next, heads and the middle part of the gut were collected and gene expression analysis was performed. We focused on clock genes per, tim to check whether clock mechanism was affected through sleep deprivation. We investigated also ninaD and npf gene expression levels to check connection between sleep level and gut function. We observed statistically significant differences in the expression of the studied genes after sleep deprivation in all studied lines. Our experiment shows that disruption of the diurnal rhythm has a negative impact on the gut-brain axis, causing irregularities in gut function at the molecular level.
Ewelina Czuba-Pakuła1, Iwona Pelikant-Małecka2, Sebastian Głowiński3, Grażyna Lietzau1, Ryszard T. Smoleński4, Przemysław Kowiański1,3
1Department of Anatomy and Neurobiology, Medical University of Gdańsk, Gdańsk, Poland
2Division of Medical Laboratory Diagnostics ‑ Fahrenheit Biobank BBMRI.pl, Medical University of Gdańsk, Gdańsk, Poland
3Department of Health Sciences, Pomeranian University of Słupsk, Słupsk, Poland
4Department of Biochemistry, Medical University of Gdańsk, Gdańsk, Poland
Abstract: Hypercholesterolemia can be encountered among the most frequent metabolic disorders coexisting with several cardiovascular and cerebrovascular diseases. The consequences of the development of hypercholesterolemia are both morphological and functional, affecting all constituents of the nervous tissue.
In this study we aimed to determine the level of activity of extracellular adenine nucleotide pathway enzymes in the murine brain microvascular endothelial cells, the blood-brain-barrier (BBB) permeability changes, and inflammatory response in brain tissue.
3-month-old ApoE-/-/LDLR-/- double knockout mice developing hypercholesterolemia, as an experimental group, and age-matching C57/BL6 mice, as a control group were used in the study. The HPLC method, immunofluorescent staining of isothiocyanate-dextran (FD40), and ELISA test were used to assess the expression of e-NTPDase, ecto-5'-NT and eADA enzymes, BBB permeability changes, and concentrations of cytokines IL-1β, IL-6, respectively. The results showed raised activity of eADA, increased FD40 leakage through the BBB and elevated levels of IL-1β and IL-6 in the hypercholesterolemic mice.
The consequences of developing hypercholesterolemia are related to the disorders of brain energy metabolism, changes in BBB permeability, and initiation of the inflammatory response. Moreover, hypocholesterolemia shifts the energy metabolism pathway towards the synthesis of inosine with immunomodulatory and neuroprotective effects, which may indicate a strong need to protect brain endothelial cells from damage and even cell death.
Zuzanna Rauk1,2, Joanna Jędrusik1, Gabriela Hatala1, Zuzanna Setkowicz1
1Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
Abstract: Traumatic brain injury (TBI) is a risk factor for the development of epilepsy and neurodegeneration, partially mediated by neuronal loss. The aim of this project was to observe the loss of various types of neurons after brain injury and identify potential sex differences.
Penetrating cortical brain injury was induced on postnatal day 30 (P30) in male and female rats. On P60 animals were perfused, brain tissue was sectioned and stained for PV (parvalbumin), NPY (neuropeptide Y), and nNOS (neuronal nitric oxide synthase). PV-, NPY-, and nNOS-expressing neurons were counted in the hippocampus, perilesional cortical area, and contralateral hemisphere of injured animals and in non-injured controls.
The analysis revealed a significantly lower number of PV-expressing neurons in deeper layers (V–VI) of perilesional cortex of females in comparison to non-injured controls, similar changes in the contralateral hemisphere, and no impact of TBI on the number of PV-expressing cells in males. NPY-expressing neurons decline was observed in medial hippocampus of both hemispheres compared to controls in male rats but not in female rats. On the other hand, more nNOS-expressing neurons were observed in perilesional cortex of injured rats of both sexes compared to controls.
To conclude, TBI affects differently various neuronal populations in both hemispheres in a sex-dependent manner.
Funding: National Science Centre Preludium 21 Grant 2022/45/N/NZ4/03028
Joanna Danielewicz1,3, Nerea Llamosas Muñozguren1, Danillo Barros de Souza3, Irene Durá1,4, Serafim Rodrigues3,5, Diego Martín Mateos1,2, Juan Manuel Encinas1,4,5
1Achucarro Basque Center for Neuroscience, Leioa, Bizkaia, Spain
2Consejo Nacional de Ciencia y Técnica (CONICET), Santa Fe, Argentina
3BCAM Basque Center for Applied Mathematics, Bilbao, Bizkaia, Spain
4University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain
5Ikerbasque, The Basque Science Foundation, Bilbao, Bizkaia, Spain
Abstract: Traumatic brain injury (TBI) can lead to a wide range of physical and cognitive impairments and it is known to impact neuronal excitability and synaptic functions. Although hippocampal impairments have been widely described following TBI, the specific effects on dentate gyrus (DG) remains to be fully understood. Here we investigated the effects of TBI on the excitability of granule cells and excitatory postsynaptic transmission in the DG at three different time periods, 3 days, 15 days and 4 months after the injury. Our results indicate that TBI does not provoke changes in passive membrane properties. By applying dimensionality reduction analysis of action potential (AP) properties, we identified the variables that exhibited significant short- medium and long-term changes. We observed that the AP half-width, AP overshoot and AP amplitude was greater in TBI cells. Moreover, the duration of afterhyperpolarization was reduced when compared to control cells. Lastly, although amplitude of sEPSC did not show differences, significant changes in frequency of sEPCS were observed in TBI cells, which did not follow the same temporal evolution as control animals. These findings indicate that at the long-term TBI increases the intrinsic excitation of granule cells and excitatory synaptic activity of the DG.
Funding: JD: Newron-TBI project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 799384. JME: PCIN-2016-128 (ERA-NET-NEURON III program), PID2019-104766RB-C21 and CPP2022-009779; and La Caixa Foundation Health Research grant HR23-00860. SR,DS,DM,JD: This research is supported by the Basque Government through the BERC 2022-2025 program and by the Ministry of Science and Innovation: BCAM Severo Ochoa accreditation CEX2021-001142-S / MICIN / AEI / 10.13039/501100011033. Moreover, the authors acknowledge the financial support received from the IKUR Strategy under the collaboration agreement between the Ikerbasque Foundation and BCAM on behalf of the Department of Education of the Basque Government. This research is also supported by the Elkartek SILICON BURMUIN (KK-2023/00090) grant.
Mervinskyi T.S.1, Grabovyi O.M.1, Savosko S.I.1, *Sokurenko L.M.1,2, Finoshkina N.Ye. 1,3,4, Rytikova N.V.1, Yaremenko L.M.1
1Department of histology and embryology, Bogomolets National Medical University, Kyiv, Ukraine
2Laboratory of Engineering, Informatics and Imaging (ICube), Integrative multimodal imaging in healthcare (IMIS), CNRS, UMR 7357, University of Strasbourg, Strasbourg, France
3Centre Éducatif "Optima", Kyiv, Ukraine
4Lycée Marie Curie, Strasbourg, France
Abstract: The effect of dexamethasone (ICH/DEX) was studied using the intracerebral hemorrhage (ICH) rats’ model on the content of non-resident mesenchymal cells in the glial scar (GS). A significant number of CD44+ cells was detected in GS ICH after 3 and 10 days, and decreased up to 60 days after the lesion. In ICH/DEX, the maximum content of these cells was observed after 30 days of the experiment. The content of CD44+ cells in GS depended on the volume of the brain lesion (p=0.037). In GS, the number of CD146+ cells was determined to be lower than CD44+ cells. CD68+ cells in GS were rarely detected, and their content did not significantly differ between ICH and ICH/DEX. CD90+ cells were only occasionally found in GS in ICH, whereas in ICH/DEX they were found in greater numbers and more often at 10 and 30 days after damage. CD44+- often, and less often CD90+- CD146+ cells had a blast-like phenotype. Thus, the number of CD44+-cells in GS depends on the brain lesion volume, and CD68+-, CD90+- and CD146+- are independent, but have a certain relationship with each other. DEX promoted persistence of CD44+ and CD146+ cells in GS.
Funding: Ministry of Health of Ukraine, state registration #0123U101051, *Lauréate scientifique du programme PAUSE 2022-2024, France
Mervinskyi Yu.V.1, Grabovyi O.M.1, Savosko S.I.1, *Sokurenko L.M.1,2, Finoshkina N.Ye. 1,3,4, Rytikova N.V.1, Yaremenko L.M.1
1Department of histology and embryology, Bogomolets National Medical University, Kyiv, Ukraine
2Laboratory of Engineering, Informatics and Imaging (ICube), Integrative multimodal imaging in healthcare (IMIS), CNRS, UMR 7357, University of Strasbourg, Strasbourg, France
3Centre Éducatif "Optima", Kyiv, Ukraine
4Lycée Marie Curie, Strasbourg, France
Abstract: The effect of dexamethasone (Dex) on neovasculogenesis in the brain perihematomal region (BPHR) was studied using a model of hemorrhagic stroke in rats. In BPHR (control), after 1-10 days, the number of cells increased rapidly, reaching a maximum on the 30th day of the experiment, and then appeared smaller after 60 days. Among them, CD133+ cells were detected. After 3 days, thin endothelial tubes formed by CD31+ cells appeared, the number of which increased until day 10. After 30 days, they acquired signs of maturity, which was manifested in their complexation with perivascular cells, and their contours often showed immunoreactivity to smooth muscle actin. With Dex action, the accumulation of BPHR cells, including CD133+ cells, was sharply reduced. The new formation of CD31+-endothelial cells tubes after 3 days of the experiment was sharply suppressed. The number of newly formed vessels in the second month was lower, but the volume of structures with the expression of smooth muscle actin in their wall was larger. Thus, Dex suppresses neovasculogenesis in BPHR, which may act as an additional factor in the development of astrogliosis, in addition to the direct effect of corticosteroids on activated astroglia.
Funding: Ministry of Health of Ukraine, state registration #0123U101051, *Lauréate scientifique du programme PAUSE 2022-2024, France
Jeremi Podsiadło1, Zuzanna Rauk1,2, Zuzanna Setkowicz-Janeczko1
1Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Sciences, Jagiellonian University, Cracow, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University, Cracow, Poland
Abstract: Background: The ketogenic diet (KD) is a type of low-carbohydrate diet in which the intake of fats significantly increases while maintaining an adequate amount of proteins, which has been identified as a potential therapy to enhance recovery after traumatic brain injury (TBI). Tractography is a 3D neuromodeling technique used for visualizing nerve tracts based on diffusion tensor imaging (DTI).
Aim: This study aimed to investigate differences in the structure of neuronal connections between injured and uninjured rat brains treated with ketogenic diet and normal diet (ND).
Methods: Rats were divided into groups obtaining a normal or ketogenic diet from postnatal day 27 (P27). On P30, penetrating brain injury was induced in the cerebral cortex in half of the animals from each group. The animals were perfused on P60, and the brains were dissected. DTI brain images were obtained and analysed using DSI Studio software.
Results: Obtained 3D models showcase a recovery improvement in KD-treated injured rats in the region of injury. Quantitive data, however, has shown overall fewer nerve tracts in KD-treated in comparison to ND-treated brains.
Conclusion: These results support evidence that KD may be a therapeutic strategy for treating TBI.
Funding: U1U/W18/NO/02.05 IDUJ
Ismail Gbadamosi1, Ilke Guntan1, Lesley Motherwell1, Izabela Lepiarz-Raba1, Dorota Dymkowska2, Ali Jawaid1
1Laboratory for Translational Research in Neuropsychiatric Disorders (TREND), Nencki Institute of Experimental Biology, Warsaw, Poland
2Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology, Warsaw, Poland
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are fatal neurodegenerative disorders with significant clinical and molecular overlaps. Cytoplasmic mislocalization and subsequent loss of nuclear functions of TAR-DNA-binding protein 43 (TDP-43) are considered critical events in the pathogenesis of ALS and FTLD. Intriguingly, conventionally unfavorable metabolic conditions, such as diabetes mellitus, are paradoxically associated with a better prognosis in ALS and FTLD, which signifies a potential role for metabolic pathways in TDP-43-associated neurodegeneration. To understand the interplay between TDP-43 and metabolic signaling in neurodegenerative contexts, we simulated TDP-43 loss of function using RNA interference in mouse NSC34 motor neurons, N2A neuroblastoma cells, and BV2 microglia. This was followed by comprehensive metabolic profiling, including metabolic flux analyses, to examine glycolysis and oxidative phosphorylation dynamics. Our findings revealed distinct cell-specific metabolic phenotypes following TDP-43 depletion. NSC34 motor neurons exhibited a hypermetabolic phenotype with accentuation of both glycolysis and oxidative phosphorylation. However, N2A cells displayed a hypometabolic phenotype, whereas BV2 microglia cells only exhibited an increase in glycolysis. These metabolic maladaptations upon TDP-43 depletion underscore the role of TDP-43 in neuronal and glial energy metabolism and provide insight into the selective vulnerability of motor neurons in TDP-43 proteinopathies.
Justyna Gargas, Justyna Janowska, Karolina Ziabska, Malgorzata Ziemka-Nalecz, Joanna Sypecka
NeuroRepair Department, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland
Abstract: The problem of neonatal hypoxia-ischemia (HI) leading to neurological dysfunction, still needs to be studied. Therapeutic hypothermia is still the only available treatment. Analysis of the secretome of glial cells subjected to oxygen-glucose deprivation (OGD, mimicking HI) brings us closer to understanding the mechanism(s) initiated by neonatal asphyxia.
The mixed glial cultures were prepared from the brains of 1-2 day old Wistar rats. Individual glial cell fractions (microglia, oligodendrocyte precursor cells/OPCs, astrocytes) were isolated and subjected to OGD as monocultures or co-cultures and cultured under serum-free and physiological normoxic conditions (5% oxygen). Supernatants conditioned by glial cells were collected and analysed for cytokine concentrations using the Luminex technique.
An approximately 8-fold increase in CXCL1 amounts was detected in supernatants conditioned by OGD-treated OPCs compared to microglial culture supernatants. Significant differences in CXCL10 levels were observed between the control and OGD groups of the glial fractions studied, particularly between those cultured alone or in co-culture. In contrast, IL-4, IL-6 and IL-10 levels showed no significant differences.
Examination of cytokine levels suggests that cells cultured as monofractions respond differently from those in co-cultures with other glial cell types, providing valuable information for basic and preclinical research aimed at testing potential drug therapies.
Funding: Supported by ESF, POWR.03.02.00-00-I028/17-00 and Statutory grant no.6 (MMRI PAS).
P. Stachowicz1, M. Frańczak1, J. M. Gargas1, A. Boratynska-Jasinska2, B. Zablocka2, J. Sypecka1
1NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
2Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
Abstract: Perinatal asphyxia results from impaired tissue oxygenation during labor, leading to hypoxia-ischemia (HI) and brain damage due to neuronal loss and abnormal glial cell function. This is one of the causes of neonatal death and a major cause of neurodevelopmental disorders in childhood. Due to the altered bioenergetics associated with HI, mitochondria are one of the potential targets for clinical intervention aimed at restoring affected neural tissue. To address this issue, a study was undertaken to evaluate mitochondrial DNA (mtDNA) content and mitochondria-located sirtuin 3 (SiRT3). Primary mixed glial cell cultures were obtained from neonatal Wistar rats and used for astrocyte isolation after 12 days. Cells cultured in physiological normoxia were subjected to oxygen-glucose deprivation (OGD) to mimic an in vitro HI insult. At 3, 24 and 72 hours after OGD, astrocytes were harvested for immunocytochemical, biochemical and molecular analyses. Determination of SIRT3 amounts in the mitochondrial fraction showed a significant increase at 24 hours after OGD (555. 48 vs 1709.91 pg/mg protein content). These changes are accompanied by an increase in the ratio of mtDNA to nuclear DNA. This suggests that mitochondria are involved in the self-defense mechanisms rather than in development of HI sequelae leading to brain damage.
Funding: Supported by National Science Center in Poland, grant: 2021/03/Y/NZ4/00214.
Marta Klimczak, Miguel García-Gabilondo, Kerrie Adrián Campbell, María Jesús García Reina, Anna Rosell Novel
Neurovascular ResearchLab, Vall d'HebronInstitut de Recerca (VHIR), Barcelona, Spain
Abstract: Stroke causes acute brain injury becoming a leading global cause of morbidity and mortality with limited treatments although it is known that neuroprotective and neurorepair mechanisms are activated spontaneously following the ischemic stroke onset in the affected tissue, including angio-vasculogenesis and neurogenesis. Post-stroke recovery in patients with neurological deficits include neuro-rehabilitative therapies to improve functional independence, but the molecular basis for rehabilitation-induced recovery remains unknown. Our hypothesis is that micro-RNAs (miRNAs) might play an important role in recovery mechanisms induced by rehabilitation and may serve as biomarkers.
To identify specific miRNAs involved in post-stroke recovery we induced permanent distal middle cerebral artery occlusion (pdMCAO) in mice (C57BL/6J, 9-11 weeks males/females) and conducted post-stroke rehabilitation by physical exercise with treadmill. Mice were divided into rehabilitation groups (RHB) of 1 and 3 weeks undergoing daily treadmill running, and corresponding groups without rehabilitation (NO-RHB) (n=12/group). TaqMan Low Density miRNA Arrays (TLDAs) were used to screen the different expression of 641 miRNAs in brain ischemic tissue at the end of the RHB/NO-RHB treatment (n=4/group). RNA extraction, reverse transcription, and preamplification using target miRNA-specific primers preceded real-time qPCR analysis. Normalization and relative expression calculations using the 2^- ΔΔCq method revealed diverse miRNA expression patterns over time and/or rehabilitation. Selected miRNAs underwent validation in the larger animal group.
Given miRNAs' pivotal role in ischemic stroke physiopathology and reparative processes, this study shows for the first time the post-stroke rehabilitation's impact on brain miRNA expression. Findings could serve as prognostic biomarkers or targets for novel ischemic stroke treatments.
Funding: STROKE-RICORS network (RD21/0006/0007) from Instituto Carlos III
AGAUR supports the Neurovascular Research Laboratory (SGR2021/0656)
Andrzej Łach, Karolina Przepiórska-Drońska, Bernadeta A. Pietrzak-Wawrzyńska, Małgorzata Kajta, Agnieszka Wnuk
Laboratory of Neuropharmacology and Epigenetics, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31–343 Krakow, Poland
Abstract: The aim of our study was to address the urgent global need for an effective strategy against acute stroke, proposing the newly designed PaPE-1 as a promising answer to limitations of existing therapeutic solutions, mainly associated with narrow therapeutic window. PaPE-1 is able to activate non-nuclear estrogen signaling, minimizing adverse hormonal effects associated with nuclear estrogen receptors signaling. Our goal was to provide evidence for PaPE-1 neuroprotective potential, including the ability to reduce necrosis and control the excitotoxicity by regulating Ca2+ flux and expression of NMDA receptors subunits – key players in stroke pathogenesis. In our study we employed a cellular model of stroke, constituted by subjecting primary neocortical cultures to 6 h of hypoxia followed by 18 h of reoxygenation. The effectiveness of the treatment was validated by a variety of biochemical and molecular assays, e.g.: AlamarBlue viability assay, LDH release, Fluoro-Jade C staining, neutral red uptake and quantifying the expression of NMDA - related genes and proteins using qPCR and ELISAs. Our research proved that post-treatment with PaPE-1 protects brain neurons against hypoxia/ischemia by inhibiting excitotoxicity and necrosis, serving as an effective therapeutic intervention against stroke.
Funding: National Science Centre of Poland, No. 2021/43/D/NZ7/00633.
Karolina Ziabska, Halina Zajac, Joanna Sypecka, Malgorzata Ziemka-Nalecz
NeuroRepair Department, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland
Abstract: Neonatal hypoxia-ischemia (HI) triggers a cascade of biochemical events including excitotoxicity, oxidative stress, and inflammation that leads to extensive brain damage manifested, among others, by the elimination of synaptic connections. Our previous studies have shown that the histone deacetylase inhibitor (HDACi)- sodium butyrate (SB) diminished inflammatory processes and reduced brain damage.
The main purpose of this study was to examine the effect of SB treatment on synapse elimination after HI.
Research included two models of neonatal hypoxic-ischemic brain injury: an in vivo study in 7 days old rats pups and an in vitro study in rats neural cells.
We observed a reduction in synaptic protein expression in rat brains after HI, which returned to control levels after SB administration. HI caused brain damage and disruption of synaptic morphology. SB treatment in HI animals decreased damage and improved tissue morphology. Furthermore, we noted a reduced number of neuronal processes in the in vitro HI model, which increased after sodium butyrate treatment.
These results suggested the neuroprotective effect of SB, as well as the protection of synaptic connections. Therefore, pharmacological modifications of complement activation could create new therapeutic approaches to reduce brain damage.
Funding: National Science Centre, Poland grant no 2017/27/B/NZ3/00582 and Mossakowski Medical Research Institute Statutory Fund no 6/2024.
Patrycja Maciak1,2, Małgorzata Duda1
1Department of Endocrinology, Institute of Zoology and Biomedical Research,
Faculty of Biology, Jagiellonian University in Krakow, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow, Poland
Abstract: Traumatic brain injury (TBI) is one of the most common causes of disability, with an annual incidence of more than 50 million cases. It is caused by a sudden injury to the brain by an external force. Research suggests that ketogenic diet (KD) may have a neuroprotective effect in this disease, although the exact mechanism is not yet understood. Produced in KD ketone bodies can be used as a substrate for cholesterol production, which then can be converted to steroids, including neurosteroids. Neurosteroids have an ability to modulate function of GABA A and NMDA receptors, making them promising candidates as potential therapeutic agents. In this study primary rat cerebral cell cultures of hippocampus and cortex were used. KD was induced by administration of beta-hydroxybutyrate and TBI was modelled by wound healing assay. Concentrations of neurosteroids pregnenolone, allopregnanolone and tetrahydrodeoxycorticosterone were measured using ELISA. The results show increased production of tetrahydrodeoxycorticosterone in cortical cells during KD treatment in TBI model compared to the uninjured group. In conclusion, this study opens up new perspectives for research into the effects of the ketogenic diet on neurosteroid production and its potential role in TBI handling.
Joanna Jędrusik1, Maciej Pudełek2, Zuzanna Setkowicz1
1Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland
2Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
Abstract: Glioblastoma multiforme (GBM) is a highly malignant tumour of the central nervous system characterized by aggressive nature and frequent emergence of drug resistance therefore making traditional treatments insufficient. Doxorubicin (DOX) as an effective and widely used chemotherapeutic agent in other types of cancer may be a candidate for the treatment of GBM. The study aims to assess the effect of doxorubicin on the invasive potential of GBM cells using animal model. For this purpose, human T98G cells were exposed to DOX for 48h followed by 7 or 14 days of recovery after drug removal and next administered into the striatum of male Wistar rats. Blood analysis showed a significant decrease in platelet count and blood urea nitrogen in the group of animals injected with T98G cells after 14 days of recovery. Distribution of tumour cells was assessed based on immunocytochemical staining of brain slices for glial fibrillary acid protein (GFAP) and human nuclear antigen (HuN) analysed with the fluorescence microscope. For precise visualisation of the cells at the injection site, 3D scans were obtained using an image deconvolution processing. Research explores the impact of doxorubicin on GBM invasiveness, providing insights into drug-resistance mechanisms and potential new treatment strategies.
Funding: The present study was financially supported by the Polish Ministry of Science and Higher Education (Diamond Grant no. 0161/DIA/2019/48 to M.P)
Mehmet Eren, Anna Garncarczyk, Natalia Bryniarska-Kubiak, Krzysztof Szade, Andrzej Kubiak
Laboratory of Stem Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
Abstract: The cytoskeleton plays a crucial role in the development and physiological functioning of neurons. Many pathological conditions (i.e. neuroinflammation) that disrupt the cytoskeleton seriously affect neuron morphology. Our research aim is to gain further insights into the impact of cytochalasin D on cellular morphology. The main purpose of our study is to examine the alterations in the morphology of neuroblastoma cells when exposed to various substances. We established our methodology with stromal cells with fluorescence microscopy imaging following ImageJ analysis. We acquired stromal cell morphology data from the control sample cell spread area was decreased control cell 192.651 µm2 to CytoD treated 129.703 µm2. The nucleus projecting area was decreased in control cells 1714.994 µm2 and the CytoD treated cells 765.4412µm2. We observed that Cyto D has a considerable effect on stromal cells' cytoskeleton development. We are applying the same methodology SH-SY5Y cell line with neuronal characteristics to address our research aim. Thanks to our research we gain important information about the contribution of cytoskeleton neuronal characteristics.
Funding: This work was financially supported by the “Student Research Project” sponsored by the Faculty of Biochemistry, Biophysics, and Biotechnology of Jagiellonian University (to M. Eren).
Mateusz Ścibiorski1, Joanna Sumorek-Wiadro1, Adriana Mika2,3, Tomasz Śledziński2, Joanna Jakubowicz-Gil1
1Department of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Poland
2Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdańsk, Poland
3Department of Environmental Analytics, Faculty of Chemistry, Gdańsk University, Poland
Abstract: Gliomas are the most malignant tumours of CNS. Due to their infiltrative nature, complete surgical resection is practically impossible, and in the course of radio- and chemotherapy, treatment resistance is very often acquired. Recent studies indicate that this process involves an increased level of very long chain fatty acids (VLCFA), which reduce the permeability of cell membranes and hinder the penetration of chemotherapy drugs into cells. The crucial role in these processes plays ELOVL1 elongase, responsible for elongation of VLCFA. Therefore, the aim of study was to investigate the effect of a specific inhibitor of ELOVL1 enzyme on the induction of programmed cell death and migration potential of gliomas.
Human glioma cells (MOGGCCM and T98G) were incubated with inhibitor for 24h. Staining with specific fluorochromes: Hoechst 33342, propidium iodide and acridine orange was used to visualize apoptosis, necrosis and autophagy. The levels of ELOVL1, ABCD1 and SCD1 proteins were determined by using Western Blot method. To determine cell viability and mobility, MTT Assay and Wound Assay were used.
The obtained results showed that the specific inhibitor of ELOVL1 enzyme effectively induced apoptosis, reduced cell viability and migration potential of both the MOGGCCM and T98G cell lines.
Bartosz Szymczak1, Maciej Klimiuk2, Joanna Wyszkowska2, Bartosz Maciejewski3, Justyna Rogalska2, Katarzyna Roszek1
1Department of Biochemistry, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, Torun, Poland
2Department of Animal Physiology and Neurobiology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, Torun, Poland
3Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, Torun, Poland
Abstract: Though the factors causing gliomas, the aggressive and fatal cancer, have not yet been identified, progress has been made in the field of understanding the glioma development. The microvesicles release is the extracellular way for cells to interact with their surroundings by paracrine regulating the rate of proliferation, migration and apoptosis. Thus, any changes in the cancer microenvironment may affect the content of microvesicles and, as a result, the rate of tumor development. While occupational exposure to extremely low-frequency electromagnetic fields (ELF-EMF) has been suspected as a brain tumor risk factor, literature reports lack consensus, and the interaction between ELF-EMF exposure and glioma-derived microvesicle release remains poorly understood. Therefore, our study focuses on changes in the microvesicles released by neurons and glioma cells exposed to ELF-EMF (50Hz, 7mT, 60min). Subsequently, untreated cells were exposed to these microvesicles. Our results show that ELF-EMF exposure increases microvesicles release. Administration of EMF-treated microvesicles decreases neuronal viability, causes changes in apoptosis rate and migration rate of gliomas. The collected data suggest that ELF-EMF exposure can potentially contribute to glioma progression by modulating microvesicle quantity and content.
Funding: Project financed by the "Excellence Initiative - Research University" program; project “Grants4NCUStudents”
Szymon Kantor1,2, Wiktoria Bielecka1, Maja Gramatyka1, Zuzanna Kozak1, Zuzanna Setkowicz1, Krzysztof Janeczko1
1Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Research,
Jagiellonian University, Kraków, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
Abstract: Epilepsy is a prevalent neurological disorder characterized by seizures originating from bioelectrical dysfunctions in hyperexcited neurons. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) act as nonclassical gaseous neurotransmitters involved in various physiological and pathophysiological processes within the central nervous system. Little is currently known regarding their role in epileptogenesis and the progression of epilepsy. Given the complexity of epilepsy and the diverse functions of gasotransmitters, we suggest a significant interplay between these phenomena.
We aim to identify the spatiotemporal activation profiles of gasotransmitter systems following pilocarpine-induced seizures in adult male Wistar rats. Our preliminary studies indicate the involvement of the brain's nitrergic system in response to seizures during the early stage of epileptic activity (up to 12 hours from onset), with rapid attenuation. Utilizing immunohistochemical labelling, our research will assess the expression levels and localization of key enzymes involved in gasotransmitter synthesis, including nNOS, iNOS, CBS, MPST, HO1, and HO2.
Reactive changes in the tissue resulting from pilocarpine-induced status epilepticus encompass widespread and time-dependent alterations originating from the piriform cortex, amygdala, and hippocampal formation, spreading to broader cortical and subcortical areas. Immunohistochemical examinations indicate the spatiotemporal changes in the expression of gasotransmitter-synthesizing enzymes during epilepsy.
Funding: This research was funded by the National Science Centre, Preludium Bis 3, grant 2021/43/O/NZ4/02208.
Nikola Gapińska1,2, Piotr Wlaź1, Marcin Jakubiec3, Michał Abram3, Krzysztof Kamiński3, Katarzyna Ciepiela3,4, Alan González Ibarra5, Dawid Krokowski5, Marek Tchórzewski5, Katarzyna Socała1
1Department of Animal Physiology and Pharmacology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin, Poland
2Doctoral School of Quantitative and Natural Sciences, Maria Curie-Skłodowska University, Lublin, Poland
3Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland
4Selvita S.A., Cracow, Poland
5Department of Molecular Biology, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin, Poland
Abstract: Glycine transporter type 1 (GlyT1) is involved in regulation of both excitatory glutamatergic and inhibitory glycinergic neurotransmission by controlling the reuptake of glycine. By changing extracellular glycine concentrations, GlyT1 inhibitors can influence the excitation/inhibition balance and thereby affect seizure susceptibility.
The aim of the study was to investigate the effect of a 2-week treatment with SSR504734, a selective GlyT1 inhibitor, on seizure thresholds in three seizure tests in mice: the 6 Hz-inducted psychomotor seizure test, maximal electroshock seizure test (MEST) and intravenous (i.v) pentylenetetrazole (PTZ) infusion test in adult male CD-1 mice. In addition, the changes in the amino acid levels in different brain structures were analyzed using the HPLC-ESI-MS technique.
We found that SSR504734 (30 mg/kg) significantly increased the threshold for the tonic hindlimb extension in the MEST but it was ineffective in the 6 Hz and i.v. PTZ-induced seizure thresholds tests. Analysis of amino acids content in brain structures showed significant increase in glycine concentration in the brainstem and increase in serine concentration in the cerebral cortex. The obtained results suggest that inhibition of GlyT1 can suppress tonic seizures.
Funding: Research project financed by the National Science Center UMO-2021/41/B/NZ7/00328.
Pervak M.P.1, Yehorenko O.S.2, Onuphrienko O.V.1, Varava S.V.1, Litvinenko M.V.3, Godlevsky L.S.1
1Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
2Simulation Medical Technologies Department, Odesa National Medical University, Odesa, Ukraine
3Histology, cytology, embryology and pathology department with the course of forensic medicine, Odesa National Medical University, Odesa, Ukraine
Abstract: The work aimed to investigate behavioral manifestations in PTZ-kindled rats under combined treatment with the histamine H3 receptor inverse agonist pitolisant and mTOR blocker rapamycin. Kindling was produced in Wistar male rats by administering three weeks of pentylenetetrazole (PTZ, 35.0 mg/kg, i.p.). tDCS of the cerebellum (500 mcA, anode, 5.0 min) and pitolisant (Selleck, 5.0 mg/kg) were treated for ten days in fully kindled rats. Behavior was investigated in the open field test. Immunohistological data - Ki67, collagen IV type, and CD34 in brain slices was quantified using the object colocalization module available in the HALO software (Indica Labs, USA). The number of crossed central squares of the kindled animals in the open field was 4.1 times less than in control rats (P<0.01). Under conditions of combined treatment with tDCS and pitolizant, the reduction of central squares crossing was 18.5% (P>0.05), while differences remained after separate drug administration. The density of Ki67, collagen IV type, and CD34 in cortical slices of kindled rats was higher by 1.75-3.5 times (P<0.01) than in the sham-stimulated control and reduced by 1.5-2.3 times after combined treatment (P<0.01). A conclusion was made that the developed treatment effectively controls neuroinflammation, which underlays chronic brain epileptization.
Funding: Research were supported by the Ministry of Health Care of Ukraine (grant N0121U114510)
Prybolovets K.O., Pastuhov O.O., Budigay N.S., Kibysh Ya.A., Godlevsky L.S.
Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
Abstract: tDCS of the cerebellum prevented PTZ-kindled seizures, and such an effect was strengthened after diazepam administration. The work aimed to investigate the pronouncement of antiseizure effects of nicotinamide and diazepam performed after preliminarily applying tDCS to the cerebellar or forebrain of PTZ-kindled rats. Kindling was induced with three weeks of PTZ (35.0 mg/kg, i.p.) administrations. Rats with generalized tonic-clonic seizures were used for the observation. Nicotinamide (100.0 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.) did not significantly reduce seizure severity. Being administered after three trials of tDCS of the cerebellum (500 mcA, anode, 5.0 min), the severity of seizures was reduced in both nicotinamide and diazepam-treated rats by 35.0% and 45.0% correspondently (P<0.01). Generalized tonic-clonic fits were prevented, and rats demonstrated myoclonuses of forelimbs and rearings. In rats with forebrain tDCS, nicotinamide administration resulted in the development of generalized seizure fits in 6 out of 9 rats (P>0.05), while the latency of seizures increased by 1.57 times (P<0.05). Diazepam (0.5 mg/kg) prevented generalized seizures in 6 out of 9 rats and reduced seizure severity by 26.5% (P<0.05). Gained data favored the heightening of sensitivity to antiseizure effects of nicotinamide and diazepam caused by anode tDCS of the cerebellum and forebrain.
Funding: Research was supported by the Ministry of Health Care of Ukraine (grant N0121U114510)
Pervak M.P.2, Al-Nadawi N.3, Kashchenko O.A.1, Bidnyuk V.K.1, Tselukh V.A.1, Aksenenko A.V.1
1Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
2Simulative Medical Technologies Department, Odesa National Medical University, Odesa, Ukraine
3Pharmacology and Pharmacognosy Department, Odesa National Medical University, Odesa, Ukraine
Abstract: The work aimed to investigate the effects of cerebellar tDCS on neurons' degeneration and microvessels' density in the brain structures of PTZ kindled rats. Kindling was produced in Wistar male rats by administration of three-week PTZ (35.0 mg/kg, i.p.). tDCS of the cerebellum (500 mcA, anode, 15.0 min) was performed before each PTZ injection. Neurons were counted with light microscopy using the object colocalization module available in the HALO software (Indica Labs, USA). The number of degenerative neurons in the frontal cortex and hippocampus (CA3) of PTZ-kindled rats by 3.4 and by 4.9 times correspondently exceeded those in the intact control group (P<0.001). The number of microvessels in the frontal cortex and the ventral hippocampus exceeded such ones in the control by 44.5% and 49.2% (P<0.05). In tDCS-treated rats, the number of degenerative neurons in the frontal cortex and ventral hippocampus was less by 1.85 and 2.30 (P<0.05) times, and the number of microvessels was less by 1.52 and 1.76 times when compared with data in kindled rats (P<0.05). Hence, data favors the pathogenic significance of neuronal loss and angiogenesis as a mechanism of chronic epileptic activity development and the effectiveness of prevention, such deteriorations with cerebellar tDCS.
Funding: Research was supported by the Ministry of Health Care of Ukraine (grant N0121U114510)
I.A.Shchehlov1, M.P. Pervak3, O.B. Poshyvak2, O.D. Ryabenka1
1Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
2Pharmacology Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
3Simulative Medical Technologies Department, Odesa National Medical University, Odesa, Ukraine
Abstract: This work aimed to investigate the level of oxidative stress markers in pentylenetetrazol (PTZ)--kindled animals and the effects of cerebellar tDCS. Kindling was produced in Wistar male rats by administration of three-week PTZ (35.0 mg/kg, i.p.). tDCS (500 mcA, 15 min) of the zone of cerebellar surface was delivered in 30 min five days before testing PTZ administration. The tissue of hemispheres was gained in two hours from the last tDCS. Spectrophotometric measurements of thiobarbituric acid reactive substances (TBARS), the activity of superoxide dismutase (SOD), and catalase were performed. tDCS prevented generalized seizures in 7 out of 8 animals (P<0.05). The level of TBARS in kindled rats with tDCS was 6.87+0.74 nmol/mg of tissue and exceeded the control value by 2.47 times (P<0.01). In kindled rats, SOD (6.53+0.72 U/mg tissue) and catalase (2.37+0.23 nM) activity were less than in the control animals by 49.6% (P<0.05) and 16.2% (P>0.05) correspondently. tDCS reduced TBARS content by 45.0% (P<0.01) and elevated SOD activity by 35.6% (P<0.05) when compared with the kindled rats. Catalase activity increased after cerebellar tDCS – up to 2.15+0.33 nM (P>0.05). Hence, the obtained data revealed the significant contribution of oxidative stress suppression to the antiseizure effects of cerebellar tDCS.
Funding: Research was supported by the Ministry of Health Care of Ukraine (grant N0121U114510).)
Arabadzhy D.R., Ryabenka O.D., Shcheglov I.A., Prybolovets K.O., Kashchenko O.A., Bidnyuk V.K.
Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
Abstract: Our work aimed to produce kindled seizures with transcorneal 6-Hz electrical stimulation (ES) (32 mA 6 Hz for 3 seconds (GRASS stimulator, Astro.Med.Inc., USA) that was performed daily 5 times per week. Altogether 25 stimulations were delivered to each rat. During ES, clonic seizures of body muscles were seen with trouble tails that were stopped immediately after ES cessation. During ES, all body's tail tonic tension and myoclonus were seen in response to each stimulus delivered. After stopping ES, no seizures were seen, and rats demonstrated intensive exploratory behavior during the first 1-5 minutes with sniffing, head nodding, horizontal and vertical locomotion, and maintenance of high tail tonus. During this period, decreased pain sensitivity was seen (one scored severity out of four score scales). Grooming was a prediction for the normalization of animal behavior. EEG registration revealed spike–wave bursts registered in the ventral hippocampus and frontal cortex from 5-10 sec up to 1.0-1.5 min after stimulation. Duration of epileptiform activity was stable in the course of the delivery of stimulations. Hence, daily performed repeated ES, no post stimulative seizures were seen, and electrographic post stimulative deteriorations were slight and did not increase with their length in the course of ES delivery.
Funding: Research was supported by the Ministry of Health Care of Ukraine (grant N0121U114510).
M.P.Pervak3, O.B.Poshyvak2, O.S.Yehorenko3, D.R. Arabadji1, S.V. Marchenko1
1Physiology and Biophysics Department, Odesa National Medical University, Odesa, Ukraine
2Pharmacology Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
3Simulative Medical Technologies Department, Odesa National Medical University, Odesa, Ukraine
Abstract: The work aimed to investigate the anxiety and depression manifestations in PTZ-kindled rats under combined treatment with the rapamycin and histamine H3 receptor inverse agonist pitolisant. Kindling was produced in Wistar male rats by administration of three-week PTZ (35.0 mg/kg, i.p.). Treatment with rapamycin (Pfizer, 0.5 mg/kg) and pitolisant (Selleck, 5.0 mg/kg) was performed for ten days in fully kindled rats. Control rats were treated with DMSO. Kindled animals spent less time (2.7 times) in the open area of the elevated plus maze (EPM) in comparison to the control (P<0.001). Following the combined administration of drugs, the period that kindled rats spent on the open arms of EPM was increased by 2.2 times compared to the control kindled rats. In the Porsolt forced swimming test, immobility response in kindled rats was higher by 37.5% (P<0.01) than in control. The immobility duration in rapamycin-treated rats remained higher by 29.0% (P<0.01) and by 23.7% (P<0.05) in rats treated with pitolisant. After combined treatment, the immobility duration in kindled rats was shorter by 33.5% (P<0.001) compared to the control. The synergy of rapamycin and pitolisant combined treatment was observed concerning abolishing in PTZ-kindled rats behavioral comorbidities such as anxiety and depression.
Funding: Research was supported by the Ministry of Health Care of Ukraine (grant N0121U114510)
Filip Kottik1, Anna Grabowska1,2, Filip Sondej1, Magdalena Senderecka1
1Institute of Philosophy, Jagiellonian University, Kraków, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Abstract: Dogmatism is commonly defined as a measure of inflexibility of thinking, unwillingness to change one’s beliefs, even when presented with contradictory evidence and rejecting evidence that does not align with preconceived notions. Higher levels of dogmatism have been linked to decreased speed of evidence accumulation.
In this study, we aimed to evaluate the association between self-reported dogmatism and evidence accumulation during performance monitoring. We investigated the relationship between dogmatism and three event-related potential components: early and late error positivity (Pe), well-validated indexes of evidence accumulation, and, on an exploratory basis, error-related negativity (ERN).
225 participants (113 females, one non-binary, mean age 23.6 years) fulfilled Altemeyer’s DOG Scale and performed a modified Flanker task, while electroencephalography signal was recorded. 20 participants were excluded from the analysis.
The results of the linear regression model revealed that the more increased the level of dogmatism, the less pronounced the late Pe. No significant associations were found between questionnaire data and other components.
Our results indicate a negative association between dogmatism and the efficiency of evidence accumulation during error monitoring. They suggest that the mental inflexibility of highly dogmatic individuals is accompanied by diminished awareness of committed errors and an underestimation of their motivational value.
Funding: The study was funded by a Sonata Bis grant (2020/38/E/HS6/00490) from the National Science Centre of Poland.
Maciej Lachowicz1; Anna Serweta-Pawlik2, Dariusz Jamro3, Grzegorz Żurek1
1Department of Biostructure, Wroclaw University of Health and Sport Sciences, Wroclaw, Poland
2Department of Occupational Therapy, Wroclaw University of Health and Sport Sciences, Wroclaw, Poland
3Department of Physical Education and Sport, General Tadeusz Kosciuszko Military University of Land Forces, Wroclaw, Poland
Abstract: The realm of electronic sports (e-sports) represents a booming sector within the digital competition landscape.
Investigating cognitive function enhancements in e-sports, this study analyzed 128 amateur e-athletes (80 males, 48 females, mean age 22.7±4.02) to understand the impact of VR training on key cognitive functions: reaction time, eye-hand coordination, concentration, alternating attention, and visuospatial memory. Participants were randomly assigned into experimental (E28) and control group (C28), with training spanning twenty-eight consecutive weekdays using the VR game 'Beat Saber.' Preliminary analysis confirmed that differences in daily gaming duration, prior e-sports experience, age, and baseline measures of cognitive functions were statistically non-significant. Statistical analysis, using Spearman Correlation, was focused on evaluating correlations between measured Cognitive Functions. Correlations were calculated at three stages: pre-training, post-training, and during a follow-up session to gauge both immediate and sustained cognitive impacts.
Study aimed to identify which cognitive functions have the highest correlations with others, suggesting their greater importance.
While the study did reveal the presence of some correlations between the cognitive functions measured, the results were unexpected. Contrary to our initial hypotheses, there were no significant correlations between concentration and reaction time, or between concentration and eye-hand coordination.
These findings challenge our initial assumptions and suggest a more complex relationship between cognitive functions than previously understood, indicating the need for further research to unravel these intricate dynamics.
Funding: The study was funded by Wroclaw University of Health and Sport Sciences
Agnieszka Rościszewska, Michał Klichowski
Cognitive Neuroscience Center, Adam Mickiewicz University, Poznan, Poland;
Learning Laboratory, Faculty of Educational Studies, Adam Mickiewicz University, Poznan, Poland
Abstract: Neurotechnology-enhanced home learning has recently gained popularity, mainly using binaural beats brain stimulation (BB). However, the impact of BB has yet to be studied in conditions other than laboratory. Thus, urgent questions are raised about what effects home-use BB (hBB) causes. Positive? Neutral? Or even negative? And if it is positive, is it not a placebo effect? Here, we conducted the world's first series of hBB experiments involving 1,500 individuals. They completed a two-part fluid intelligence test at home. While taking the second part, there were several acoustic conditions, such as listening to binaural beats or other sounds and just silence. In the first study, we investigated whether the postulated results of hBB were not due to the placebo effect. The second investigation allowed us to compare hBB effects with cognitive responses to the remaining acoustic stimulation. Both showed that hBB can dramatically deteriorate cognitive effectiveness. However, in the third, we found that hBB may increase fluid intelligence, but only in particular groups of people with specified personality traits. In other words, we have found that most people generally lose by using hBB. Still, there is a small group of people, which we characterize here, who gain from it.
Funding: During this project A.R. and M.K. were supported by European Cooperation in Science and Technology grant: European Network on Brain Malformations (Neuro-MIG) (COST Action CA16118). COST is supported by the EU Framework Programme for Research and Innovation Horizon 2020. A.R. was also a scholarship holder granted by the Foundation of the Adam Mickiewicz University, Poznan, for the academic year 2022/2023.
Bartłomiej Panek1,2, Izabela Szumska3,4, Dariusz Asanowicz1*, Rob van der Lubbe2,6
1Institute of Psychology, Jagiellonian University, Krakow, Poland
2Faculty of Physics, Adam Mickiewicz University, Poznan, Poland
3Department of Cognitive Psychology University of Economics and Human Sciences in Warsaw, Warsaw, Poland.
4Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland.
5Faculty of Behavior, Management, and Social Sciences, University of Twente, Enschede, The Netherlands
Abstract: When sensory-guided actions must be performed under time pressure (TP), a trade-off arises between the accuracy of the choice and the time required to make the decision. This trade-off is evident in behavioral studies, where prioritizing speed often leads to more impulsive responses and a higher likelihood of errors. Traditional decision models explain effects of TP through the lowering of a fixed threshold, which terminates the decision process. However, these models leave an open question: At which stage of processing does TP affect neural activity, particularly in tasks that require target selection? To address this issue, we measured the electroencephalogram (EEG) and the electromyogram (EMG) during the flanker task, which required selecting a target among distracting flankers under different TP conditions. The results revealed, that both time pressure (TP) and flanker congruency influenced theta (4-8Hz) activity in sensorimotor (SMC) and midfrontal (MFC) cortex. In contrast, theta power over occipital cortex (OCC) was only modulated by congruency. With regard to phase connectivity, TP increased theta coherence between the SMC and MFC, whereas congruency modulated ipsilateral connections between the SMC and OCC. Our findings challenge the fixed-threshold perspective, favoring a more nuanced view where TP impacts the neural activity at multiple levels and stages.
Funding: Supported by grant from the National Science Center in Poland (NCN-project: UMO-2012/05/B/HS6/03806, UMO-2019/33/B/HS6/00096)
Paweł Basoń1, Anna Grabowska1,2, Filip Sondej1, Magdalena Senderecka1
1Institute of Philosophy, Jagiellonian University, Kraków, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Abstract: Previous research has indicated a significant relationship between religious fundamentalism and error monitoring. The aim of this study was to validate these findings and to examine whether this association is influenced by the need for cognitive closure (NFC). Electroencephalography recordings were obtained from 378 healthy participants from different religious backgrounds during a Go/NoGo task. The analysis focused on the well-established biomarker of error monitoring, error-related negativity (ERN), along with self-reported NFC and fundamentalism. Correlation analysis confirmed a significant relationship between fundamentalism and ERN (r = -.12, p < .05), and revealed a significant association between NFC and fundamentalism (r = .10, p < .05); the correlation between NFC and ERN was not significant. While the moderation effect of NFC on the association between fundamentalism and ERN was not significant overall (p = .09), it became significant when only Christians (n = 234) were considered. Specifically, the relationship between fundamentalism and ERN was moderated by both general NFC (β = -1.36, p < .05) and two of its subconstructs: preference for predictability (β = -.99, p < .05) and intolerance of ambiguity (β = -1.14, p < .01). Our study confirmed that the higher religious fundamentalism, the more intense error monitoring. Furthermore, the moderation effect of NFC was limited only to Christian group, where a higher level of NFC strengthens the association between fundamentalism and error monitoring.
Funding: This study was supported by the National Science Centre of Poland, grant 2020/38/E/HS6/00490.
Marcin Skotniczny1, Anna Grabowska1,2, Filip Sondej1, Magdalena Senderecka1
1Institute of Philosophy, Jagiellonian University, Kraków, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Abstract: There is ongoing debate on whether believing in free will or thinking of the world as deterministic influence our behavior. Various studies have shown that deterministic beliefs impact not only our actions, but also basic neurocognitive processes such as response monitoring. Well established biomarkers of response monitoring are correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe). The aim of our study was to investigate associations between these components and believing in free will and determinism. Two hundred twenty three volunteers (112 females, one non-binary, mean age 23.7 years) filled the Nadelhoffer’s Free Will Inventory and performed a modified version of Flanker task while their electroencephalographic signal was recorded. Using multiple linear regression models, we found that the stronger the belief in free will, the higher the magnitude of CRN. Moreover, we observed that the higher the level of determinism, the lower the amplitude of Pe. There were no significant associations between beliefs and ERN. Our results indicate that individuals with a strong belief in free will are less certain about correctness of their actions, whereas individuals with a strong belief in determinism are less emotionally concerned about their errors. They also suggest that basic neurocognitive processes related to response monitoring are influenced by whether people believe they can exert intentional control over their actions.
Funding: The study was funded by a Sonata Bis grant (2020/38/E/HS6/00490) from the National Science Centre of Poland.
Kachynska Tetiana1, Kuznietsov Illia1, Zhuravlov Oleksandr1, Zasiekina Larysa1, Hlova Iryna1, Kovalenko Oksana1
1Laboratory of Aging neurophysiology, Human and animal physiology department, Lesya Ukrainka Volyn National University, Lutsk, Ukraine
Abstract: The neural manifestations of moral injury (MI) remain poorly studied and not well separated from the effects of posttraumatic stress disorder (PTSD). If the differences between MI and PTSD conditions exist, they plausibly can be revealed in the analysis of brain states. The method of brain microstates (MS) looks promising for detecting brain states, specific for MI. In our study, 36 subjects, who lived in Ukraine during the first year of the Russian-Ukrainian war, non-combatants, took part. To assess the level of psychological stress, the following psychological tests were used: PCL-5 (PTSD), GAD-7 (general anxiety), PHQ-9 (depression), MISS-M-SF (moral injury). EEG was recorded during eyes closed rest state using a 21-channel EEG system. EEG data were processed with LORETA software, and MS maps were calculated for 4 microstates. Obtained MS indices (transition rates, transition probabilities, MS durations) were analyzed using generalized linear models approach. It was found that transition rates of the microstate B correlate with MISS-M-SF results, while there were no correlations between MS data and responses to other questionnaires. Microstate B is associated with the visual networks activity, and may reflect different levels of activation of visual imagination depending on MI severity.
Korolczuk, I.1,2, Burle, B.2, Coull, J.T.2, Ogińska, H.3, Ociepka, M.4,5, Senderecka, M.4, & Śmigasiewicz K.2
1Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
2Centre for Research in Psychology and Neuroscience (UMR7077), Aix-Marseille University & CNRS, Marseille, France
3Institute of Applied Psychology, Jagiellonian University, Kraków, Poland
4Institute of Philosophy, Jagiellonian University, Kraków, Poland
5Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Abstract: In unpredictable contexts, error monitoring typically increases, suggesting a greater subjective cost for maladaptive responses to uncertain events. We explored whether temporal unpredictability amplifies error monitoring using a temporally cued stop-signal task. Symbolic cues predicted (temporally predictable) or not (temporally unpredictable) the target onset. Participants had to inhibit responses in 25% of trials signaled by an auditory tone presented shortly after target onset. Enhanced detection of inhibitory errors was evident, reflected in prolonged motor time (MT), the interval between the onset of the muscle activity and mechanical response that indexes an online detection and an attempt to stop erroneous actions. Likewise, the error-related negativity (ERN), an electrophysiological marker of response outcome evaluation, increased following inhibitory errors in temporally unpredictable conditions. In conclusion, our EMG and EEG findings underscore that the cost of failing to inhibit actions in a temporally unpredictable environment is significantly higher.
Funding: This work was supported by the National Science Centre of Poland grant (2018/31/N/HS6/00633) awarded to Inga Korolczuk.
Giansalvo Barbalinardo and Mirosław Wyczesany
Instytut Psychologii, Wydział Filozoficzny, Uniwersytet Jagielloński, Krakow, Poland
Abstract: Nowadays, the abundance of technological devices has established an enormous utilization of multimedia sources of stimulation, resulting, especially in young individuals, in the well-known trend of media multitasking (MM). This attitude is reflected in a compulsive consumption of more than one media stream simultaneously or in their usage during the involvement in non-media activities. Findings so far seem to point out a somewhat mixed scenario, documenting various associations, binding the MM with attentional performance. The research project here preseneted is aimed to comprehensively characterize the attentional functioning of media multitaskers (MMs) brain, by availing of the effective connectivity analysis based on electroencephalography (EEG). 69 participants were recruited on purpose to record brain EEG signal, while performing tasks in selective and divided attention condition. The final scope was to asses their perfomance in each task condition and merge them with the interplay among neural substrates related to attention, namely: the dorsal attentional (DAN) and the ventral attentional networks (VAN) - connected respectively with the voluntary and the stimulus-driven attentional cntrol - and the fronto-parietal (FPN) and the cingulo-opercular networks (CON), sustaining the DAN and VAN fuctioning, monitoring and modulating attentional processes.
Paulina Wąsowska-Dean and Dominika Pietrzak, Karolina Radziuk, Agnieszka Merta
Department of Biological Psychology, Center for Behavioral Neuroscience, Psychology Institute, SWPS University,
Warsaw, Poland
Abstract: The magnitude of cognitive load is defined by the current capacity of working memory, i.e., the size of cognitive resources in relation to the stimulating value of the task and the environment in which it is performed. Measurements of the cardiovascular system are considered particularly effective indicators of cognitive load due to their reliability and the possibility of continuous recording. The aim of the study was to assess the relationship between the magnitude of cognitive load and the activation of the autonomic nervous system. The participants were male and female psychology students (n = 20, age M = 23). The participants were asked to perform a modified Sternberg task. They were asked to memorize a sequence of two or six digits. After some time, a single digit appeared on the screen. Participants judged whether it had been shown in the preceding sequence. The research tools consisted of: PsychoPy Program, Electrocardiograph, and Svarog. The data were analysed using the t-Student test. Based on the results obtained, it can be concluded that the task involving memorizing a longer sequence of digits was associated with greater cognitive load and greater activity of the autonomic nervous system - with a faster heart rate (t(19) = 3.858; p < 0.001; d = 0.865). The results of the study confirm the hypothesis. Cognitive load is associated with an increase in arousal (an increase in the activity of the autonomic nervous system).
Funding: SWPS UNIVERSITY
Oliwia Polok1, Anna Grabowska1,2, Filip Sondej1, Magdalena Senderecka1
1Institute of Philosophy, Jagiellonian University, Kraków, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Abstract: Procrastination involves delaying necessary tasks, often engaging in substitute activities that are not essential. Research indicates that procrastination is associated with dysfunctions in emotional regulation and cognitive control, including attentional processes, response inhibition, and error monitoring. The aim of our research was to validate these associations using the stop signal task. We collected electroencephalographic recordings from 225 participants (113 women, 1 non-binary, mean age 24 ± 4.18 years) and assessed self-reported procrastination using the 40-item Procrastination Assessment Questionnaire.
The analysis revealed that procrastination is associated with amplitudes of sensory P1 (r = 0.134, p = .045) and attentional P2 (r = 0.146, p = .028) components, time-locked to the go stimulus, as well as with mean go response time (RT) (r = -0.141, p = .035). Additionally, it is correlated with mean RT in failed inhibition trials (r = -0.160, p = .016) and inhibition rate (r = -0.126, p = 0.059). However, procrastination is not associated with stop-signal- and response-related components. These results suggest that increased levels of procrastination are linked to stronger perceptual processing and attentional binding to the go stimulus; resulting in shorter RTs but a lower inhibition rate. Although individuals higher in procrastination do not exhibit weakened processing of stop signals and monitoring responses on the neural level, their increased orientation towards go stimuli leads to more inhibitory errors.
Funding: The study was funded by a Sonata Bis grant (2020/38/E/HS6/00490) from the National Science Centre of Poland.
Szymanek Kaja1, Witkowska Magdalena1,2, Cacek Jakub1,2, Bielski Krzysztof1,2, Wichary Szymon1
1Institute of Psychology, Jagiellonian University, Cracow, Poland
2Doctoral School of Social Sciences, Jagiellonian University, Cracow, Poland
Abstract: Complex decision-making requires strategic processing of information. Two strategies have been established: Take The Best (TTB) and Weighted Additive Rule (WADD). TTB relies on the most significant information, while WADD is based on the consideration of all available information. We hypothesize that WADD is strongly associated with inhibitory control, which, according to the literature, is embedded in the functioning of the right inferior frontal gyrus (rIFG) and presupplementary motor area (preSMA). In order to investigate the involvement of those areas in decision-making strategies utilizing, we conducted a study with 34 healthy participants (Mage = 25) who completed decision-making tasks in three transcranial magnetic stimulation (TMS) sessions targeting preSMA, rIFG, or parietal cortex as sham stimulation. We found that TMS stimulation of preSMA, but not rIFG, impacts strategy preference in this task, such that under preSMA stimulation, participants adapted better to the conditions of the task. Additionally, the need for cognitive closure moderated this effect, so that it was noticeable only in participants with low values on the need for cognitive closure scale. We discuss these results in light of theories of the functional role of preSMA which might be crucial for processing complex information during decision-making.
Funding: Supported by National Science Centre, Poland, grant no. 2019/35/B/HS6/01173.
Ewa Wiwatowska1, Magdalena Pietruch1,2, Magdalena Prost1, Jan Mizerka1,3, Jan Glapiak1, Jarosław Michałowski1
1Poznan Laboratory of Affective Neuroscience, SWPS University, Poznan, Poland
2Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Warsaw, Poland
3Adam Mickiewicz University, Poznan, Poland
Abstract: Procrastination is the irrational delay of task completion. Previous studies have demonstrated that procrastinating students present difficulties in attentional control and performance monitoring, which could be observed in both behavioral and neurophysiological indices. Moreover, our recent research showed that these dysfunctions might be modulated by norm-referenced feedback received in the task. In the present study we wanted to replicate these findings as well as investigate the influence of positive and negative norm-referenced feedback on the frequency and emotional valence of mind-wandering episodes experienced during task completion. To achieve this goal, we recruited high (HP) and low procrastinating (LP) students (N= 143), who completed the go/no-go task with thought probes. Obtained results indicated that HP (vs LP) participants more frequently reported negatively valenced task-unrelated thoughts, regardless of received feedback. Moreover, in the HP group, negative (but not positive) feedback resulted in decreased reaction time variability, which is the behavioral index of attentional control. This effect was not observed among LP students. What is interesting, previously found differences between HP and LP individuals in neurophysiological indices of attention and performance monitoring were not apparent in the current study. This suggests that procrastination-related cognitive dysfunctions might depend on the motivational factors.
Funding: This research was supported by a grant from the National Science Center (Narodowe Centrum Nauki, NCN) to the first author Ewa Wiwatowska (decision number: 2021/41/N/HS6/02832).
Natalia Afek1 and Dmytro Harmatiuk2, Magda Gawłowska3, Krystyna Golonka3, Sergii Tukaiev4, Anton Popov2, Tadeusz Marek5
1Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
2Department of Electronic Engineering, Igor Sikorsky Kyiv Polytechnic Institute, Kyiv, Ukraine
3Institute of Applied Psychology, Jagiellonian University, Kraków, Poland
4Università della Svizzera italiana, Institute of Public Health, Lugano, Switzerland
5Faculty of Psychology, SWPS University, Katowice, Poland
Abstract: The chronic occupational stress is associated with pronounced decline in emotional and cognitive functioning. The studies on neural mechanisms indicate significant changes in brain activity and altered patterns of event-related potentials among burnout participants.
This study presents the analysis of resting-state brain functional connectivity. Data were collected from a 256-channel EEG system. The sample consisted of 50 burnout employees and 50 controls matched on age, gender and occupation (Mean age = 36.03, SD = 8.07; 60 women). The functional connectivity between burnout and control participants was tested in eyes-closed (EC) and eyes-open (EO) conditions using resting state paradigm.
The results indicate significant differences in brain activity between burnout and control group. Resting-state network of the burnout group is characterized by decreased functional connectivity in right frontal areas, consistently in all analyzed bands (1-35 Hz) and consistent tendency of increased connectivity in fronto-parieto-occipital and temporal areas in theta1, theta2 and lower alpha (alpha1) bands. Moreover, our analyses for the first time point to distinctive aspects of functional connectivity within alpha3, beta1, and beta2 subbands in the burnout syndrome. These findings provide insights into the neurobiological underpinnings of burnout and its associations with altered resting-state networks.
Agnieszka Fudali-Czyż¹, Marta Szewczyk², Lukas Grzeczkowski³
¹Department of Neurocognitive Psychology, Institute of Psychology, University of the National Education Commission, Krakow, Poland
²Department of Experimental Psychology, Institute of Psychology, The John Paul II Catholic University of Lublin, Poland
³Department of Psychology, Institute of Psychology, Lukas Grzeczkowski, Humboldt University of Berlin, Germany
Abstract: Slower responses to targets presented in the left visual field can be a result of fatigue. More evidence for this comes from research on covert attention (without eye movements). We tested whether attentional asymmetry differs between selective and non-selective covert and overt attention. We used the eye fixation-related potentials (EFRP) paradigm. The task of 23 right-handed subjects (aged 20-30 years) was to indicate whether the target T is rotated to the left or right side. The letter was displayed alone (non-selective attention) or appeared surrounded by distractors (Ls) (selective attention). The stimuli appeared 4 degrees from the center of the screen and could be perceived without saccades (covert attention, n=256 trials) or 11 degrees from the center of the screen, forcing the participant to make saccades to notice them (overt attention, n=256 trials). Reactions were faster to the right targets only in covert attention, regardless of the selectivity conditions. In overt attention, we found shorter saccades to the left side and the posterior P1 larger from the right than from the left electrodes for the right targets. We relate these results to the functions of inhibiting and enhancing processing by the left and right hemispheres in different attentional conditions.
Wiktoria Orłowska 1,2, Renate Rutiku 1
1Consciousness Lab, Institute of Psychology, Jagiellonian University, Krakow, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Krakow, Poland
Abstract: TOne of the challenges of studying conscious perception stems from the lack of a widely recognized measure for comparing subjective experiences with objective task processing within the same performance dimension. Past research has primarily relied on objective task outcomes (such as accuracy or reaction times) contrasted with subjective judgments (like confidence ratings or the Perceptual Awareness Scale). However, those measures capture entirely different aspects of the task.
Here we use a novel behavioral measure of conscious perception to demonstrate how a specific stimulus presentation enables both objective and subjective comparisons within a single task dimension, namely time. In this new type of task, participants are presented with a stimulus whose state is continuously changing. Their goal is to report the state of the stimulus when they first saw it appearing on the screen. Behavioral findings reveal a consistent tendency among participants to overestimate the starting point of the stimulus. After testing the primary form of the procedure with nearly 250 participants, we proceeded to gather additional data employing various experimental setups.
The results confirm that, across all of those tasks, there is a systematic disparity in the reported (subjective) and actual (objective) initial state of the continuously changing stimulus, revealing an average delay of 136 ms in participants' perception of stimulus onset. A subsequent follow-up experiment, evaluating participants' capacity to recall the stimulus state from memory, clarifies that this observed effect cannot solely be attributed to an inability to provide accurate responses.
Importantly, the LAG exhibits a surprisingly strong dissociation from objective task performance indices such as reaction times. Thus, we conclude that this discrepancy in estimation may signify a delay in becoming aware of the stimulus, which we term the "LAG of consciousness".
Funding: National Science Center Poland grant (grant number 2021/42/E/HS6/00425)
