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CSF1 overexpression has pleiotropic effects on microglia in vivo
Author(s) -
De Ishani,
Nikodemova Maria,
Steffen Megan D.,
Sokn Emily,
Maklakova Vilena I.,
Watters Jyoti J.,
Collier Lara S.
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22717
Subject(s) - microglia , biology , glial fibrillary acidic protein , macrophage colony stimulating factor , microbiology and biotechnology , neuroglia , lipopolysaccharide , receptor , genetically modified mouse , in vivo , central nervous system , neuroinflammation , cytokine , downregulation and upregulation , macrophage , inflammation , immunology , transgene , neuroscience , in vitro , gene , biochemistry , immunohistochemistry
Macrophage colony stimulating factor (CSF1) is a cytokine that is upregulated in several diseases of the central nervous system (CNS). To examine the effects of CSF1 overexpression on microglia, transgenic mice that overexpress CSF1 in the glial fibrillary acidic protein (GFAP) compartment were generated. CSF1 overexpressing mice have increased microglial proliferation and increased microglial numbers compared with controls. Treatment with PLX3397, a small molecule inhibitor of the CSF1 receptor CSF1R and related kinases, decreases microglial numbers by promoting microglial apoptosis in both CSF1 overexpressing and control mice. Microglia in CSF1 overexpressing mice exhibit gene expression profiles indicating that they are not basally M1 or M2 polarized, but they do have defects in inducing expression of certain genes in response to the inflammatory stimulus lipopolysaccharide. These results indicate that the CSF1 overexpression observed in CNS pathologies likely has pleiotropic influences on microglia. Furthermore, small molecule inhibition of CSF1R has the potential to reverse CSF1‐driven microglial accumulation that is frequently observed in CNS pathologies, but can also promote apoptosis of normal microglia. GLIA 2014;62:1955–1967