Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations.

Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models. However, how does prenatal VPA exposure affect microglia remains to be elucidated. The triggering receptor expressed on myeloid cells 2 (TREM2) is revealed to be implicated in a range of microglia functions. However, reports on the association between TREM2 and VPA-induced ASD rat models are scarce. Our results showed that prenatal VPA exposure induced autistic-like behaviors, downregulated the levels of TREM2, up-regulated microglial activation, dysregulated microglial polarization, and altered synapse in offspring. TREM2 overexpression partly ameliorated microglia dysfunction and autistic-like behaviors in prenatal VPA-exposed rats. Our findings demonstrated that prenatally VPA exposure is likely to cause autistic-like behavior in the rat offspring via TREM2 down-regulation to affect the microglial activation, microglial polarization and synaptic pruning of microglia for the first time.