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Combination of Growth Factors Enhances Remyelination in a Cuprizone-induced Demyelination Mouse Model

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Abstract

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.

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Acknowledgments

The authors are grateful to Poonam Sachan and Sarah L. Daniels for their technical assistance and Donna Crandall for her assistance in the preparation of figures. This work was funded by National Institute of Health NICHD grant HD-06576.

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Authors and Affiliations

  1. Departments of Neurobiology and Psychiatry, Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Neuroscience Research Building, 635 Charles E. Young Drive South, Room 379, Los Angeles, CA, 90095-7332, USA

    Shalini Kumar, Juan Carlos Biancotti & Jean de Vellis

  2. Department of Physiology, University of Tokyo, Tokyo, Japan

    Masahiro Yamaguchi

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  1. Shalini Kumar
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  2. Juan Carlos Biancotti
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  3. Masahiro Yamaguchi
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  4. Jean de Vellis
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Correspondence to Jean de Vellis.

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Special issue dedicated to Dr. John Blass.

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Kumar, S., Biancotti, J.C., Yamaguchi, M. et al. Combination of Growth Factors Enhances Remyelination in a Cuprizone-induced Demyelination Mouse Model. Neurochem Res 32, 783–797 (2007). https://doi.org/10.1007/s11064-006-9208-6

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  • DOI: https://doi.org/10.1007/s11064-006-9208-6

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