We have previously reported that mice prenatally exposed to valproic acid (VPA) at embryonic day 12.5 exhibit autism spectrum disorder (ASD)-like phenotypes such as social deficits and cognitive impairment, and reduced dendritic spine density in the hippocampal CA1 region. Several studies show that enriched environment (EE) ameliorates some abnormal behaviors in ASD rodent models, but it is unclear whether EE improves cognitive impairment. Here, we examined the effects of early EE on ASD-like phenotypes and neuromorphological changes in prenatal VPA-exposed mice. Mice were housed for 4 weeks from 4 weeks of age under either a standard environment or EE. EE increased BDNF mRNA levels in the hippocampus of both control and VPA-exposed mice. In addition, the EE improved social deficits and cognitive impairment, but not hypolocomotion, in VPA-exposed mice. Prenatal VPA exposure caused decreases in hippocampal mRNA levels of PSD-95 and Shank2, in addition to loss of dendritic spines in the hippocampal CA1 region. The EE improved these hippocampal changes. These findings suggest that the EE improved most ASD-like phenotypes including cognitive impairment in the VPA-exposed mice by enhancing dendritic spine function.

To: 要旨(抄録)