Is-4: Role of Endogenous Neural Precursor Cells in Multiple Sclerosis (Pages: 5-5)


Baron-Van Evercooren AS *, Tepavcevic V , Nait-Oumesmar B , Spigoni G ,

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Objective: In the adult brain, microenvironments that maintain a source of neural stem cells and NPCs are the SVZ of the lateral ventricle and the DG of the hippocampus. Experimental demyelination and MS, reactivate the SVZ, leading to increased proliferation, oligodendrogenesis and ectopic migration to periventricular white matter. The goal of this paper is to review the importance of specialized cellular niches showing plasticity regarding cell number, fate decision, migration and differentiation in the context of demyelinating pathologies such as multiple sclerosis (MS). Materials and Methods: Various tracing paradigms in combination with stem cell markers have allowed to study reactivation of the adult stem cell niches in a number of disease animal models going from rodents to non-human primates and MS tissues. Results: Tracing studies indicate that while -B cells are the SVZ source of newly formed oligodendrocytes in normal conditions, -A and -C cells undergo a functional switch in response to demyelination to increase oligodendrogenesis. Specialized cell-cell interactions occur within the niche, suggesting ongoing communication within the different cell types and namely specialized interactions between ependymal cells and B cells. Gaining more insights in the modulation of these interactions in animal models, could help to understand how the niche is reactivated in response to inflammatory demyelination. Maintaining the balance between neural stem cells and NPCs in the SVZ niche is critical to supply the brain with specific neural populations, both under normal or demyelinating conditions. Several factors influencing SVZ homeostasis were elucidated and found to play a crucial role in regulating the balance between neural stem cells and NPCs as well as neurogenic and oligodendrogenic NPCs. Some of these mechanisms are perturbed in response to chronic inflammation leading to enhanced SVZ thickness, increased oligodendrogenesis at the expense of neurogenesis. Furthermore, -A and -B cells are vulnerable to chronic inflammation, further contributing to a diminished neuronal renewal in the OBs and resulting in olfactory deficits. A major question concerns the nature of the molecular cues involved in the correct targeting of the migrating NPCs to the OBs. These include growth factors, cell adhesion molecules, integrins, chemokines and repellents. While, growth factors and chemokines were identified as major players in ectopic recruitment of SVZ cells to lesion sites, little is known on the role of other molecular cues in directing NPCs and derivatives to the lesion site. Conclusion: In spite of the demonstration of the adult SVZ reactivation in experimental models and MS, mobilization, differentiation and oligodendrocyte recruitment remain limited. Therefore, understanding the mechanisms regulating the biology of the stem cell niches in normal and pathological conditions could help in designing therapeutic strategies preventing the loss of NPCs and promoting their proliferation, migration and differentiation for myelin diseases such as MS.