Microglial GPR56 is the molecular target of maternal immune activation-induced parvalbumin-positive interneuron deficits.

ABSTRACT: Parvalbumin-positive (PV⁺) interneurons play a critical role in maintaining circuit rhythm in the brain, and their reduction is implicated in autism spectrum disorders. Animal studies demonstrate that maternal immune activation (MIA) leads to reduced PV⁺ interneurons in the somatosensory cortex and autism-like behaviors. However, the underlying molecular mechanisms remain largely unknown. Here, we show that MIA down-regulates microglial Gpr56 expression in fetal brains in an interleukin-17a-dependent manner and that conditional deletion of microglial Gpr56 [Gpr56 conditional knockout (cKO)] mimics MIA-induced PV⁺ interneuron defects and autism-like behaviors in offspring. We further demonstrate that elevated microglial tumor necrosis fa

SUBMITTER: Yu D 

PROVIDER: S-EPMC9075805 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature