Exploring the oligovascular niche in CNS remyelination. (360G-Wellcome-096415_Z_11_Z)

Remyelination is the process by which new myelin sheaths are restored to demyelinated axons. It involves the regeneration of new oligodendrocytes by a population of widespread multipotent adult neural stem cells called oligodendrocyte precursor cells (OPCs). There are three keys phases: first, OPC activation (initial critical changes in gene expression); second, OPC recruitment (proliferation and migration); third, differentiation into myelin-forming oligodendrocytes. Each stage is regulated by a complex interplay of environmental signals and cell intrinsic mechanisms. While many of the elements of this regulatory network have been explored the effects of the vasculature and especially new blood vessel formation remains unknown - a surprising gap given the role of angiogeneis in other regenerative processes and the proliferative effects of endothelial cells on OPCs in vitro. This one-year project will start with a description of the vascular changes associated with the remyelination of a well-characterized model of CNS demyelination using immunohistochemistry and transcriptome analysis, relating these to OPCs dynamics. It will end with a preliminary functional study on the OPCs effects of experimental manipulation of angiogenesis. The project is designed to provide grounding in laboratory-based neurobiology that will form the basis of further more detailed and technically demanding studies.