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Urszula Wojda
Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
Abstract: Circulating miRNAs in blood plasma present significant potential for use as presently unavailable minimally-invasive biomarkers for diagnosis of aging-related diseases, such as cancer or Alzheimer’s disease (AD). Recently we identified a panel of 6 dysregulated miRNAs in blood plasma of patients with early AD (Patent EP3449009). Here we applied RT-qPCR, the most sensitive and inexpensive analysis method of circulating miRNA, for verification studies in a new cohort of 50 AD patients and 50 healthy control subjects. As current methods of identifying optimal normalisers are lacking in their evaluation of the stability of normalizers in aging population, we created a novel, transparent, method for selecting optimal normalisers in aging population. The obtained data showed significant differences for all tested panel miRNAs in their plasma levels in AD patients, confirming chosen miRNAs as minimally-invasive diagnostic biomarkers for AD. Moreover, we recommend the standard protocol for assessment of plasma miRNA levels in an aging population employing a novel set of normalizers.
Funding: Work supported by the Polish National Science Centre grant OPUS 2018/29/B/NZ7/02757 and by the EU Horizon2020 FETOPEN grant no 737390 (ArrestAD).
Natalia Pudełko-Malik1, Dominika Drulis-Fajdasz2, Dariusz Rakus2, Piotr Młynarz1
1Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wroclaw, Poland 2Department of Molecular Physiology and Neurobiology, University of Wroclaw, Sienkiewicza 21, Wroclaw, 50-335, Poland
Abstract: The phenomenon of used metabolomics approaches, especially nuclear magnetic resonance (NMR) spectroscopy, is not only about identification and quantification of all metabolites in biological samples, but also allows visualization of the actual metabolic state of living organisms studied at a particular point in time (Mielko et al. 2021). This unique feature distinguishes metabolomics from other omics studies like genomic, transcriptomic, and proteomics (Emwas et al. 2013). It is generally known that the metabolic coupling of astrocytes and neurons plays a key role in the phenomenon of plasticity of neural networks and the formation of memory tracks (Suzuki et al. 2011). Use of NMR method to analyze the image of the physiology of nervous tissue at different ages is quite attractive and the observed changes between chosen metabolites, in compared animal groups, may give new information about changes in cognitive abilities and the formation of new memory traces implicated with age.
Anna Mietelska-Porowska, Justyna Domańska, Angelika Więckowska-Gacek, Andrew Want,
Dominik Chutorański, Urszula Wojda
Neurobiology Center, Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
Abstract: An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor of Alzheimer's disease (AD) but the holistic view of the interacting processes through which such diet may contribute to AD pathogenesis is missing. This presentation will provide an overview of the evidence demonstrating that WD-associated systemic alterations drive impairment of the blood-brain barrier (BBB) and development of neuroinflammation paralleled by accumulation of toxic amyloid. Later these changes are followed by dysfunction of synaptic transmission, neurodegeneration and finally memory and cognitive impairment. The mounting results indicate that WD can trigger AD by acceleration of inflammaging, and that BBB impairment induced by metabolic and systemic inflammation play the central role in this process. This overview of the sequential, complex pathomechanisms initiated by WD, which can lead from peripheral disturbances to neurodegeneration, can support future prevention strategies.
Funding: This work was financed by the National Science Centre, Poland, projects No. 2018/29/N/NZ7/01724, and 2014/15/D/NZ4/04361.
Adam Krzystyniak1,Malgorzata Wesierska2, Gregory Petrazzo1, Agnieszka Gadecka1, Magdalena Dudkowska1, Anna Bielak-Zmijewska1, Grazyna Mosieniak1, Iza Figiel3, Jakub Wlodarczyk3, Ewa Sikora1
1Laboratory of Molecular Basis of Aging, Nencki Institute of Experimental Biology Polish Academy of Science, Warsaw, Poland
2Laboratory of Neuropsychology, Nencki Institute of Experimental Biology Polish Academy of Science, Warsaw, Poland
3Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology Polish Academy of Science, Warsaw, Poland
Abstract: Aging is associated with cognitive decline and accumulation of senescent cells which could be targeted by senolytics such as Dasatinib and Quercetin (D+Q). We studied the effect of senolytics on multifactorial aging-related cognitive dysfunctions by testing male Wistar rats in the active allothetic place avoidance task. Our studies revealed that 8 week-long treatment with D+Q decreased peripheral inflammation measured by the levels of serum inflammatory mediators (including SASP factors) in aged rats which coincided with long lasting (at least 6 weeks) alleviation of learning deficits and memory impairments observed in aged animals. We also observed changes in the dendritic spine morphology of the apical dendritic tree from the hippocampal CA1 neurons upon D+Q treatment and changes in the trimethylation level of histone H3 isolated from the hippocampus. Our results support the notion that senolytics on alleviating age associated cognitive dysfunctions.
Funding: Narodowe Centrum Nauki (UMO-2019/35/B/NZ4/01920)
