Increased expression of colony-stimulating factor-1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss

Glia. 2018 Oct;66(10):2108-2125. doi: 10.1002/glia.23464. Epub 2018 Aug 25.


Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice. Immunohistochemical studies demonstrated that CSF1 was expressed in astrocytes and neurons in normal mouse spinal cord. In acute EAE, CSF1 expression was significantly increased, especially in astrocytes in peripheral white matter and large motoneurons. High density of activated microglia was observed in the gray matter where motoneurons expressed high-level CSF1 in acute EAE. Significant large motoneuron loss was seen in chronic EAE and the remaining motoneurons with high-level CSF1 were enwrapped by microglia. Viral vector mediated over-expression of CSF1 in spinal neurons induced profound proliferation and activation of microglia at the injection site and microglia enwrapped CSF1-transduced neurons and their neurites. Significant loss of large CSF1-transduced neurons was seen at 2 and 3 weeks post-viral injection. Demyelination in the CSF1-transduced areas was also significant. These results implicate that CSF1 upregulation in CNS may play an important role in the proliferation and activation of microglia in EAE, contributing to neuroinflammation and neurodegeneration. © 2018 Wiley Periodicals, Inc.

Keywords: colony-stimulating factor-1; experimental autoimmune encephalomyelitis; interleukin-34; lentiviral vector; microglia; multiple sclerosis; neuronal death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cell Proliferation / physiology
  • Chronic Disease
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Gene Expression Regulation
  • Gray Matter / metabolism
  • Gray Matter / pathology
  • HEK293 Cells
  • Humans
  • Interleukins / metabolism
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Male
  • Mice
  • Microglia / metabolism*
  • Microglia / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • White Matter / metabolism
  • White Matter / pathology


  • Interleukins
  • interleukin-34, mouse
  • Macrophage Colony-Stimulating Factor