Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination.
New CNS neurons and glia are generated throughout adulthood from endogenous neural stem and progenitor cells. These progenitors can respond to injury, but their ability to proliferate, migrate, differentiate, and survive is usually insufficient to replace lost cells and restore normal function. Potentiating the progenitor response with exogenous factors is an attractive strategy for the treatment of nervous system injuries and neurodegenerative and demyelinating disorders. Previously, we reported that delivery of leukemia inhibitory factor (LIF) to the CNS stimulates the self-renewal of neural stem cells and the proliferation of parenchymal glial progenitors. Here we identify these parenchymal glia as oligodendrocyte (OL) progenitor cells (OPCs) and show that LIF delivery stimulates their proliferation through the activation of gp130 receptor signaling within these cells. Importantly, this effect of LIF on OPC proliferation can be harnessed to enhance the generation of OLs that express myelin proteins and reform nodes of Ranvier in the context of chronic demyelination in the adult mouse hippocampus. Our findings, considered together with the known beneficial effects of LIF on OL and neuron survival, suggest that LIF has both reparative and protective activities that make it a promising potential therapy for CNS demyelinating disorders and injuries.
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Benjamin E
BE
Deverman
Paul H
PH
Patterson
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology*; D011901:Ranvier's Nodes / Q000473:pathology / Q000502:physiology; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*
D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse