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Macrophage-colony stimulating factor as an inducer of microglial proliferation in axotomized rat facial nucleus

  1. Shinichi Yamamoto1,
  2. Kazuyuki Nakajima1,2,
  3. Shinichi Kohsaka2

Article first published online: 12 OCT 2010

DOI: 10.1111/j.1471-4159.2010.06996.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Special Issue: Introducing Preclinical Systematic Reviews

Volume 115, Issue 4, pages 1057–1067, November 2010

Additional Information

How to Cite

Yamamoto, S., Nakajima, K. and Kohsaka, S. (2010), Macrophage-colony stimulating factor as an inducer of microglial proliferation in axotomized rat facial nucleus. Journal of Neurochemistry, 115: 1057–1067. doi: 10.1111/j.1471-4159.2010.06996.x

Author Information

  1. 1

    Department of Bioinformatics, Faculty of Engineering, Soka University, Tokyo, Japan

  2. 2

    Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan

*Address correspondence and reprint requests to Kazuyuki Nakajima, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan. E-mail: nakajima@t.soka.ac.jp

Publication History

  1. Issue published online: 21 OCT 2010
  2. Article first published online: 12 OCT 2010
  3. Accepted manuscript online: 11 SEP 2010 09:38PM EST
  4. Received April 23, 2010; revised manuscript received September 1, 2010; accepted September 3, 2010.

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Keywords:

  • cFms;
  • M-CSF;
  • microglia;
  • PCNA;
  • proliferation;
  • transection of facial nerve

J. Neurochem. (2010) 115, 1057–1067.

Abstract

We analyzed the mechanism of microglial proliferation in rat axotomized facial nucleus (axotFN). In immunoblotting analysis for possible mitogens, we noticed that the amounts of macrophage-colony stimulating factor (M-CSF) increased in the axotFN for 3–7 days after transection. In contrast, the amounts of granulocyte macrophage-CSF and interleukin-3 did not significantly increase. A potential source for M-CSF was immunohistochemically verified to be microglia. Immunoblotting showed that the amounts of receptor for M-CSF (cFms) increased in the axotFN for 3–14 days after injury, and immunohistochemical staining showed that cFms is expressed in microglia. Proliferating cell nuclear antigen as a marker of proliferation was immunohistochemically identified in microglia in axotFN, and the level was found to peak 3 days after transection in immunoblotting. Hypothesizing that up-regulated M-CSF triggers the above phenomena, we investigated the effects of M-CSF on cFms and proliferating cell nuclear antigen levels in primary microglia. The biochemical experiments revealed that M-CSF induces cFms and drives the cell cycle in microglia. The neutralization of M-CSF in microglia derived from axotFN significantly reduced the proliferation. These results demonstrate that up-regulated M-CSF triggers the induction of cFms in microglia and causes the microglia to proliferate in the axotFN.

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