26.04.2026, Sunday, 10:30-12:00
General focus of the symposium:
Neuroinflammation and disrupted lipid signalling are central contributors to pathology in demyelinating and neurodegenerative diseases such as multiple sclerosis (MS). This symposium explores multiple mechanistic domains, including the immunomodulatory effects of serotonergic and sigma-1–active compounds, oxysterol–EBI2 signalling as well as mechanosensitive ion channel Piezo1 and 2 signalling in immune regulation and myelination, and the therapeutic potential of APRIL in modulating acute CNS inflammation. We will also explore lipid-directed transcriptional networks in CNS homeostasis and strategies for targeted drug delivery to the brain. Together, these studies aim to uncover pathways capable of modulating neuroimmune interactions, promoting tissue repair and enhancing therapeutic efficacy in MS. Psychedelic compounds engage 5-HT2A, sigma-1, NMDA, and other receptors involved in neuroimmune regulation. Dimethyltryptamine (DMT) acts as a potent immunomodulator, reducing LPC-induced NF-κB signalling and cytokine release, protecting against demyelination, and suppressing inflammation-driven oligodendrocyte precursor cell (OPC) activation in cerebellar slices. In endothelial cells, DMT counteracts VCAM1 induction and modulates junctional genes, supporting blood–brain barrier integrity. Oxysterol 7α,25-dihydroxycholesterol (7α,25OHC), the endogenous ligand for EBI2 (GPR183), promotes remyelination and regulates lipid metabolism. In cerebellar cultures, 7α,25OHC modulates LXRβ and canonical LXR targets even in EBI2-deficient tissue, while EBI2 activation redistributes lymphocytes, reducing peripheral levels and increasing splenic accumulation. Mechanosensitive Piezo channels influence OPC maturation and myelination, with inhibition protecting against demyelination and activation reducing myelin integrity. Amyloid beta stress in Alzheimer’s disease similarly impairs OPC and oligodendrocyte function, highlighting shared vulnerabilities. AAV-mediated expression of APRIL in cortical neurons mitigates microgliosis and demyelination, activating pathways linked to inflammatory modulation and tissue repair. Importantly, APRIL acts locally to modulate acute CNS inflammation without detectable systemic toxicity, highlighting its therapeutic potential. Collectively, these findings illuminate convergent molecular and physiological mechanisms regulating neuroimmune signalling, lipid metabolism, remyelination, and drug delivery, offering a foundation for the development of next-generation therapeutics for MS.
10:30 Dr hab. Aleksandra Rutkowska
Medical University of Gdańsk
"Oxysterol-Driven Modulation of Lymphocyte Dynamics Mimics Key Mechanisms of Action of Leading Therapies for Multiple Sclerosis"
Oxysterols acting through the EBI2 (GPR183) receptor pathway are emerging as regulators of immune cell trafficking and CNS repair. We investigated the main endogenous EBI2 ligand, oxysterol 7α,25-OHC, and found that its administration markedly reduced circulating lymphocytes while at the same time increasing their accumulation in the spleen, without inducing cell toxicity. This pattern of lymphocyte redistribution resembles key mechanisms shared by several high-efficacy disease-modifying therapies (DMTs) for multiple sclerosis (MS), suggesting that targeting EBI2–oxysterol signalling may represent a therapeutically relevant immunomodulatory axis. Complementary analysis of cerebrospinal fluid and serum from MS patients provide further support for the involvement of oxysterols in the pathophysiology of MS.
Together, these findings identify oxysterol-mediated modulation of lymphocyte dynamics as a safe and promising immunoregulatory mechanism with potential relevance for MS and other immune-mediated conditions. Ongoing analyses in human samples aim to validate these results and further define their applicability to therapeutic development.
11:10 Fatimah Zahra
Medical University of Gdańsk, Department of Anatomy and Neurobiology, Gdańsk, Poland
"Molecular Crosstalk Between EBI2 and LXR Signalling and Their Effect on Neuroimmune Regulation and Myelination"
7α,25-dihydroxycholesterol (7α,25OHC) is an oxysterol and agonist of Epstein Barr virus-induced gene 2 (EBI2; GPR183), a receptor that regulates innate and adaptive immune responses in the periphery and CNS. 7α,25OHC accelerates remyelination in the cuprizone model and upregulates the synthesis of multiple lipid classes. Oxysterols also activate liver X receptors (LXRs), which modulate cholesterol metabolism and inflammatory signaling.
To investigate whether 7α,25OHC influences LXR pathways, organotypic cerebellar slices from wild type and EBI2 knockout mice were demyelinated and treated with 7α,25OHC, with or without LXR antagonists.
Exogenous 7α,25OHC increased LXRβ expression and regulated canonical LXR targets, including ABCA1 and SREBP1c, even in EBI2-deficient slices, indicating EBI2 independent signaling.
These findings suggest that 7α,25OHC reshapes oxysterol metabolism and broader signaling networks in the CNS, highlighting its potential as a modulator of lipid-mediated pathways relevant for remyelination and neuroinflammation.
11:23 Piotr Pobiarzyn
Medical University of Gdańsk, Department of Anatomy, Division of Anatomy and Neurobiology
"Mechanosensitive Piezo Ion Channels and Amyloid Beta Pathology in the Regulation of Oligodendrocyte Function and Myelination"
Piezo channels are mechanosensitive ion channels that translate mechanical stimuli into intracellular signaling and are enriched in white-matter regions. Evidence indicates that Piezo1/2 may regulate oligodendrocyte maturation and myelin stability: inhibition appears protective in demyelination models, while activation is linked to myelin disruption. Alzheimer’s disease also involves marked white-matter pathology, and both OPCs and mature oligodendrocytes are vulnerable to amyloid beta (Aβ). These observations suggest that Piezo signaling and Aβ-related stress may converge on pathways controlling myelination, potentially contributing to white-matter degeneration.
This project will examine how Piezo channels influence OPC differentiation and myelin formation and whether Aβ alters these processes through disrupted mechanotransduction. It further aims to identify shared molecular mechanisms and test whether Piezo modulation can preserve oligodendrocyte function under AD-relevant conditions
Primary OPCs and cerebellar slices will be studied under controlled mechanical conditions with pharmacological or genetic modulation of Piezo activity, alongside exposure to oligomeric and fibrillar Aβ. Responses will be evaluated using calcium imaging, signaling assays, and myelin-marker analysis, with pathway-focused transcriptional profiling. Functional relevance will be assessed in neuron–glia co-cultures to determine effects on myelination.
Piezo activation is expected to impair OPC maturation, whereas inhibition may promote differentiation. Aβ will likely exacerbate mechanosensitive stress signaling, revealing overlapping pathways related to calcium dynamics and cellular structure. Targeting Piezo could partially rescue myelination deficits.
Defining the interaction between Piezo signaling and Aβ toxicity may clarify mechanisms underlying white-matter vulnerability in Alzheimer’s disease and highlight Piezo channels as potential targets for protecting oligodendrocyte function.
11:36 Leonardo Ricciardi
1. Bio-Imaging Lab, University of Antwerp, 2610 Wilrijk, Belgium. 2. μNEURO Research Centre of Excellence, University of Antwerp, 2610 Wilrijk, Belgium. 3. Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute.
"AAV-mediated Delivery of a Proliferation Inducing Ligand (APRIL) to Cortical Neurons Limits Inflammation and Demyelination in the Corpus Callosum of the Cuprizone Mouse Model"
A Proliferation-Inducing Ligand (APRIL) is a tumour necrosis factor superfamily member with multiple effector roles in the peripheral and central nervous system (CNS). In the CNS, APRIL helps maintain immune homeostasis and supports neuronal survival, yet whether it can therapeutically modulate acute neuro-inflammatory and neurodegenerative processes is unclear.
To investigate this in a severe neuro-inflammatory context, we tested whether local APRIL delivery can influence microglial/astrocytic responses and demyelination in the cuprizone (CPZ) mouse model of neuro-inflammation and demyelination.
We applied adeno-associated virus (AAV)–mediated gene transfer to drive APRIL expression by cortical neurons positioned directly above the splenium of the corpus callosum. Following CPZ intoxication, we evaluated microglial and astrocytic activation and myelin content by in vivo T2 and diffusion magnetic resonance imaging (MRI) and validated them by post-mortem quantitative immunohistochemistry (IHC) and bulk transcriptomic and proteomic profiling.
T2 and diffusion MRI, corroborated by quantitative IHC, demonstrated that secretion of APRIL by cortical neurons attenuated CPZ-induced microglial recruitment and demyelination in the splenium, but not in the cortex. Integrated transcriptome-proteome analysis of splenium and cortex, further supported by IHC, highlighted astroglial lipid-metabolic circuitry - marked by the astrocytic fatty-acid-binding protein 7 (Fabp7) - as a candidate axis underlying APRIL’s effects to reduce inflammatory cell recruitment and myelin preservation.
AAV-mediated expression of APRIL by cortical neurons counteracted microglial recruitment and demyelination in the splenium of CPZ-treated mice. Together, our findings provide a framework for the mechanistic dissection of APRIL’s therapeutic potential and further translational evaluation in CNS pathologies characterised by acute neuro-inflammatory responses.
11:49 Olga Blauth
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Laboratory of Neuromuscular Plasticity
"Distinct Transcriptional Signatures of Motorneuron Fate in Response to Neonatal Nerve Regeneration or Degeneration"
Peripheral nerve injuries during early postnatal life frequently result in limited axonal regrowth and extensive motoneuron degeneration, in contrast to the regenerative capacity observed in adults. Understanding the cellular mechanisms underlying this developmental difference is critical for improving neonatal nerve repair strategies.
To identify spinal cord cellular responses and transcriptional programs that distinguish successful regeneration from regenerative failure following neonatal peripheral nerve injury.
We employed a sciatic nerve grafting model in newborn rats, in which an older donor nerve fragment (P6) was transplanted into a younger recipient (P3), thereby leveraging the donor tissue's more advanced developmental state to enhance regeneration. In contrast, grafts from age-matched donors (P3/P3) fail to support effective regrowth. We also applied single-nucleus RNA sequencing (snRNA-seq) together with immunohistochemistry to define injury-driven shifts in spinal cord cell populations and transcriptional responses.
Given the absence of robust neonatal motoneuron markers, this approach provided an unbiased framework to resolve cell-type-specific injury programs across the spinal cord. Enhanced regeneration was associated with increased survival of ChAT⁺ motoneurons, whereas failed regeneration correlated with motoneuron degeneration. snRNA-seq revealed distinct injury-responsive transcriptional states across multiple cell types. Notably, regenerative conditions exhibited an early increase in Iba1⁺ microglial cells, whereas degenerative conditions showed delayed and prolonged microglial activation.
Together, these findings suggest that injury-induced microenvironmental cues and neuroimmune dynamics critically shape regenerative capacity and motoneuron survival following neonatal peripheral nerve injury.
Chairman: Małgorzata Dąbrowska-Bovijn
