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Fetal toll-like receptor 3 signalling contributes to the induction of autism-like behaviors in a mouse model of maternal immune activation

ABSTRACT: A mouse model of maternal immune activation (MIA) is commonly used to study neurodevelopmental disorders. Gene expression analysis has suggested that fetal brain macrophages may be activated by MIA, but it is unclear whether these transcriptional changes connect to behavioral phenotypes in offspring. Here, we have shown that the induction of autism spectrum disorder (ASD)-like behavioral phenotypes by MIA in male offspring is dependent upon fetal activation of the toll-like receptor 3 (TLR3) signaling molecule TRIF. Using single-cell RNA sequencing, we identified a cluster of border-associated macrophages (BAMs) that was significantly enriched in wild-type fetal brains following TLR3-MIA but not diminished in Trif -/- fetal brains. Moreover, after TLR3-MIA, the number of fetal BAMs in the choroid plexus, but not in the meninges, was increased, and these cells were characterized by increased S100a8/9 expression. Finally, we proposed that activation of fetal TLR3-TRIF signaling was induced by transplacental viral infection. Overall, our data suggest that fetal TLR3 signaling contributes to MIA-induced ASD-like behavioral phenotypes in mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE196151 | GEO | 2022/02/08

REPOSITORIES: GEO

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