末梢神経再ミエリン化に対する低酸素誘導性転写因子の役割

抄録

Myelin sheath is essential for the rapid propagation of action potentials and proper functions of the nervous system. In the peripheral nervous system, it has been well-known that Schwann cells generate myelin sheath through several stepwise differentiation processes, but the detailed mechanism to regulate Schwann cell differentiation remains unclear. Previously, we demonstrated the involvement of hypoxia-inducible factor 1α (HIF1α) in the regulation of peripheral myelination. To further investigate the role of HIF1α in peripheral myelination, we used a conditional knock-out (cKO) mice lacking HIF1α gene in myelinating Schwann cells. An in vitro myelination assay revealed that hypoxic treatment facilitated myelination in wild-type control but not cKO. Unexpectedly, peripheral myelin of cKO mice was formed normally without significant motor deficits. Next, we examined the remyelination of cKO peripheral nerves after injury and found that the number of myelinated axons after nerve injury was decreased compared with that in control nerves. These findings suggest that HIF1α might be involved in peripheral remyelination after injury. To reveal the regulatory mechanism of HIF1α in peripheral myelination, we are performing  the comprehensive analysis of HIF1α regulated gene expression in Schwann cells.