Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain

Atsuki Kawamura, Yoshifumi Abe, Fumiko Seki, Yuta Katayama, Masaaki Nishiyama, Norio Takata, Kenji F. Tanaka, Hideyuki Okano, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

Abstract

CHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) in oligodendrocyte lineage-specific Chd8 heterozygous mutant mice. DTI revealed that ablation of Chd8 specifically in oligodendrocytes of mice was associated with microstructural changes of specific brain regions including the cortex and striatum. The extent of these changes in white matter including the corpus callosum and fornix was correlated with total contact time in the reciprocal social interaction test. Analysis with rsfMRI revealed changes in functional brain connectivity in the mutant mice, and the extent of such changes in the cortex, hippocampus, and amygdala was also correlated with the change in social interaction. Our results thus suggest that changes in brain microstructure and functional connectivity induced by oligodendrocyte dysfunction might underlie altered social interaction in mice with oligodendrocyte-specific CHD8 haploinsufficiency.

Original languageEnglish
Article number160
JournalMolecular brain
Volume13
Issue number1
DOIs
Publication statusPublished - 2020 Dec

Keywords

  • Autism spectrum disorder
  • CHD8
  • Diffusion tensor imaging
  • Functional connectivity
  • Oligodendrocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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