[Abstract Title]. - Society for Neuroscience

Support: B. Deverman is supported by a fellowship from CIRM
National Institute of Neurological Disorders and Stroke
Title: Exogenous LIF stimulates oligodendrocyte progenitor cell proliferation and remyelination
in vivo
Authors: *B. E. DEVERMAN 1 , S. BAUER 2 , P. H. PATTERSON 1 ;
1 California Inst. Tech., Pasadena, CA; 2 Physiologie Neurovégétative, UMR 6153 CNRS, 1147
INRA, Univ. P. Cézanne-Aix-Marseille-3, Marseille, France
Abstract: The development of therapies that enhance the repair capabilities of the adult brain by
stimulating the proliferation of endogenous neural stem and progenitor cells and/or directing
their subsequent differentiation into functional neurons and glia is a relatively neglected area of
current stem cell research. We have found that injection of an adenovirus expressing leukemia
inhibitory factor (LIF) into the adult brain promotes neural stem cell (NSC) self-renewal and
stimulates the proliferation oligodendrocyte progenitor cells (OPCs). Based on these findings, in
particular the effect of LIF on OPCs, we hypothesized that if LIF could enhance the OPC
response in the context of chronic demyelination it may, in turn, promote the generation of new
oligodendrocytes and aid remyelination. To test this, we have been feeding mice a diet
containing cuprizone for 12 weeks, a course of treatment that induces demyelination in the
corpus callosum (CC), hippocampus, and cortex, and injecting the mice with either a LIF- or
lacZ-expressing adenovirus (Ad-LIF or Ad-lacZ) in the lateral ventricle. Three weeks after
adenovirus injection and removal of cuprizone from the diet, mice that received Ad-LIF exhibit
an increase in the number of proliferating OPCs in the demyelinated hippocampus. Many of
these OPCs survive and differentiate so that by 6 weeks after removal of cuprizone, the number
of mature oligodendrocytes in LIF-treated mice is restored to near normal numbers in the CA3
region of the hippocampus, where LIF-induced Stat3 activation is the greatest. Remarkably,
remyelination in the CA3 region is more extensive in LIF-treated mice and is accompanied by
the reformation of nodal, paranodal, and juxtaparanodal domains on a subset of axons. Our
findings that LIF can promote oligodendrocyte generation and remyelination in vivo taken
together with its known ability to protect oligodendrocytes from death in the EAE model of MS,
as well as following spinal cord injury, suggest that LIF has multiple activities that could be of
therapeutic benefit for demyelinating diseases.
Disclosures: B.E. Deverman , None; P.H. Patterson, None; S. Bauer, None.
Poster
251. Demyelinating Disorders: Animal Models and Human Studies I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm