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Exogenous Leukemia Inhibitory Factor Stimulates Oligodendrocyte Progenitor Cell Proliferation and Enhances Hippocampal Remyelination

Deverman, Benjamin E. and Patterson, Paul H. (2012) Exogenous Leukemia Inhibitory Factor Stimulates Oligodendrocyte Progenitor Cell Proliferation and Enhances Hippocampal Remyelination. Journal of Neuroscience, 32 (6). pp. 2100-2109. ISSN 0270-6474. PMCID PMC3561904. http://resolver.caltech.edu/CaltechAUTHORS:20120313-142825780

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1523/JNEUROSCI.3803-11.2012DOIArticle
http://www.jneurosci.org/content/32/6/2100PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561904/PubMed CentralArticle
Additional Information:© 2012 the authors. Received July 25, 2011. Revision received December 1, 2011. Accepted December 16, 2011. This work was supported by a fellowship to B.E.D. from the California Institute for Regenerative Medicine and by grants from the National Institute of Neurological Disorders and Stroke (NS045744 and ARRANS45744) and the McGrath Foundation. We thank Sylvian Bauer for thoughtful discussions and assistance initiating this study; Tania Banerji for technical assistance; Elaine Hsiao, Jan Ko, Natalia Malkova, and Puja Saluja for critical reading of this manuscript; and members of the California Institute of Technology Office of Laboratory Animal Resources, especially N. Miyamoto, for consistent excellent animal care. We also thank W. Muller and W. Richardson for the generous gifts of transgenic mouse lines. Author contributions: B.E.D. and P.H.P. designed research; B.E.D. performed research; B.E.D. and P.H.P. analyzed data; B.E.D. and P.H.P. wrote the paper. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
California Institute for Regenerative MedicineUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)NS045744
National Institute of Neurological Disorders and Stroke (NINDS)ARRANS45744
McGrath FoundationUNSPECIFIED
PubMed Central ID:PMC3561904
Record Number:CaltechAUTHORS:20120313-142825780
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120313-142825780
Official Citation:Benjamin E. Deverman and Paul H. Patterson Exogenous Leukemia Inhibitory Factor Stimulates Oligodendrocyte Progenitor Cell Proliferation and Enhances Hippocampal Remyelination The Journal of Neuroscience, 8 February 2012, 32(6):2100-2109; doi:10.1523/JNEUROSCI.3803-11.2012
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29705
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:14 Mar 2012 15:07
Last Modified:30 Dec 2015 22:21

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