Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain.
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.
['Kawamura|Atsuki|A|', 'Abe|Yoshifumi|Y|', 'Seki|Fumiko|F|', 'Katayama|Yuta|Y|', 'Nishiyama|Masaaki|M|', 'Takata|Norio|N|', 'Tanaka|Kenji F|KF|', 'Okano|Hideyuki|H|', 'Nakayama|Keiichi I|KI|0000-0002-7185-1529']
D000818:Animals D001522:Behavior, Animal D001921:Brain D019070:Cell Lineage D004268:DNA-Binding Proteins D056324:Diffusion Tensor Imaging D006579:Heterozygote D051379:Mice D008817:Mice, Mutant Strains D009154:Mutation D009415:Nerve Net D009836:Oligodendroglia D012919:Social Behavior
CHD8 Oligodendrocyte Functional connectivity Autism spectrum disorder Diffusion tensor imaging