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In Response to Damage Activated Microglia Enhance Neuronal Differentiation and Survival
Author(s) -
Chen Jing,
Shibata Annemarie
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.537.1
Subject(s) - microglia , neun , neuroprotection , neuroscience , biology , neurogenesis , pi3k/akt/mtor pathway , neurotrophic factors , microbiology and biotechnology , nestin , neurodegeneration , brain derived neurotrophic factor , inflammation , signal transduction , stem cell , immunology , medicine , neural stem cell , pathology , immunohistochemistry , biochemistry , receptor , disease
Contribution of microglia to neurogenesis under different pathological conditions is unclear. Both pro and anti‐neurogenic effects have been reported, reflecting the complexity and heterogeneity of microglial activation and effects. In this study, we have developed an in vitro model system designed to co‐culture microglia in transwells suspended above mechanically damaged or undamaged primary neuronal cultures. Immunocytochemistry, Western blot, and RT‐PCR analysis of damaged neurons co‐cultured with microglia at specific time points indicates developmentally regulated expression of nestin, α‐internexin, GFAP, β‐tubulin III, and NeuN when compared to damaged neurons that were not co‐cultured with microglia. Analysis of co‐cultures also shows increased activation of the PI3K/AKT and MAPK signaling pathways suggesting microglial secretion may utilize these pathways to promote neuronal differentiation and survival. Further we are examining neurotrophic microglial induced changes in neuronal epigenetics through the targeting of histone modifications and transcription factors such as REST and co‐REST. Our data suggests that microglia may possess modifiable properties to become potential targets for neuroprotective therapies. Research is funded by NIH grant number P20 RR016469 from the INBRE Program of the National Center for Research Resources.