Strategies of myelin regeneration with optogenetically controlled glial cells

Abstract

Microglia, macrophage-like cells in the CNS, are multi-functional cells; they play an important role in removal of dead cells or their remnants by phagocytosis in the CNS degeneration as well as are one of important cells in the CNS cytokine network. They are thought to be originated from mesoderm, and to be similar cells to other tissue-resident macrophages. As macrophages, activated microglia have been shown to remove potentially deleterious debris and promote tissue repair by secreting neurotrophic factors at the neuronal injury sites, however, they can release potentially cytotoxic substances in vitro, and at least so-called fully activated form of microglia which are observed at the injury site in AIDS dementia is neurotoxic. These suggest that some factor (s) may contribute to change microglial phenotype from protective to toxic, but the detail is not clear. Recently we generated channelrhodopsin-mutant protein expressing microglia, Ra2-GR and 6-3-GR. Channelrhodopsin is an ion channel activated by light irradiation. Intracellular sodium ion increased by light irradiation in both Ra2-GR and 6-3-GR accompanied by increase of mRNA expression such as pro-inflammatory cytokines, chemokines and iNOS. This technique can control microglial activation, therefore, it may provide a new strategy for repair/regeneration of neural and oligodendrocytic damages.