Dr. William Hodos NACS Seminar: Dr. Toby Merson

Modulation of remyelination efficiency following cuprizone-induced demyelination

CNS demyelination is a hallmark of several neurological and neurodegenerative diseases, an archetype being multiple sclerosis (MS). Studies with MS subjects suggest that the efficiency of remyelination following a demyelinating episode is correlated with improved clinical prognosis. On this basis, it is believed that clinical interventions that potentiate remyelination efficiency are likely to significantly improve disease outcomes. We have explored the effects of ageing, growth factor infusion and voluntary exercise on the generation of new myelin-forming oligodendrocytes in a mouse model of demyelination induced by cuprizone challenge. In particular, we have explored the differential effects of interventions on remyelination mediated by oligodendrocyte progenitor cells (OPCs) and oligodendrogenic neural precursor cells (NPCs) that derive from the ventricular-subventricular zone. Our data reveal that NPC-derived oligodendrocyte regeneration declined dramatically with ageing, but this reduction was at least partially reversed by co-infusion of epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) via the cisterna magna. We also demonstrate that voluntary wheel running following demyelination enhances functional remyelination, via differential effects on oligodendrogenesis mediated by OPCs and NPCs. Together our data indicate that modulation of progenitor responses by extrinsic modifiers could hold therapeutic potential for improving remyelination efficacy after a demyelinating insult.

Dr. Toby Merson is a Staff Scientist at NIH National Institute of Mental Health.

Dr. William Hodos NACS Seminars are free and open to the public.