RRC ID 81438
Author Takanezawa Y, Tanabe S, Kato D, Ozeki R, Komoda M, Suzuki T, Baba H, Muramatsu R.
Title Microglial ASD-related genes are involved in oligodendrocyte differentiation.
Journal Sci Rep
Abstract Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.
Volume 11(1)
Pages 17825
Published 2021-9-8
DOI 10.1038/s41598-021-97257-9
PII 10.1038/s41598-021-97257-9
PMID 34497307
PMC PMC8426463
MeSH Animals Autism Spectrum Disorder / genetics* Autism Spectrum Disorder / metabolism Brain / cytology Brain / drug effects Brain / metabolism Cell Differentiation / drug effects Cell Differentiation / genetics* Cytokines / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Gene Expression Insulin-Like Growth Factor I / genetics Insulin-Like Growth Factor I / metabolism Lipopolysaccharides / pharmacology Mice Microglia / cytology Microglia / drug effects Microglia / metabolism* Neural Stem Cells / cytology Neural Stem Cells / drug effects Neural Stem Cells / metabolism Oligodendroglia / cytology Oligodendroglia / drug effects Oligodendroglia / metabolism* Phagocytosis / drug effects Phagocytosis / genetics Tuberous Sclerosis Complex 2 Protein / genetics Tuberous Sclerosis Complex 2 Protein / metabolism
Resource
DNA material pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)