Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model.
Loss of oligodendrocytes (OLs) is often associated with demyelination. PDGF-AA, bFGF, NT3 and IGF-1 are known to regulate OL proliferation, survival and/or differentiation. Following cuprizone-induced demyelination in mice a combination of above four growth factors (GF) was intracranially injected to stimulate remyelination in vivo. Activation of cell signaling and transcription factors involved in cell proliferation, survival and differentiation was observed in response to GF. Increased cell proliferation and migration occurred in corpus callosum, lateral ventricles, rostral migratory stream and cerebri at 2-5 days post injection (dpi) of GF cocktail. The fate of these newly formed nestin or bromodeoxyuridine (BrdU) positive progenitors was traced to proteoglycan NG2 and glutathione transferase (GST) pi positive cells, early and mature OL lineage markers, respectively. Immunostaining for myelin showed the presence of more myelinated fibers in GF-injected brains at 21 dpi. Remyelination in response to GF was confirmed by electron microscopy. In conclusion, this combination of GF is a promising tool to consider for remyelination strategies.
Kumar
Shalini
S
Department of Neurobiology, Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California-Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7332, USA.
Biancotti
Juan Carlos
JC
Yamaguchi
Masahiro
M
de Vellis
Jean
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004032:Diet; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D014158:Transcription, Genetic
D002614:Chelating Agents; D036341:Intercellular Signaling Peptides and Proteins; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D003471:Cuprizone; D007334:Insulin-Like Growth Factor I