Reduced protein expressions of cytomembrane GABA A Rβ3 at different postnatal developmental stages of rats exposed prenatally to valproic acid.

Decreased inhibition plays an extremely important role in pathogenesis of autism spectrum disorder (ASD). Therefore, we aimed to determine whether expression levels of the γ-aminobutyric acid type A receptor β3 subunit (GABAA Rβ3), K+ -Cl- cotransporter 2 (KCC2), and Na+ -K+ -Cl- cotransporter 1 (NKCC1) related to inhibition transmission are changed in a sodium valproate-induced rat model of ASD. Decreased expression levels of membrane GABAA Rβ3 (m-GABAA Rβ3) and KCC2 as well as increased endocytosis of GABAA Rs were found in the model group. However, there were no significant differences in expression of total GABAA Rβ3 and NKCC1 between the control and model groups. In addition, we observed growth retardation, impaired spatial memory, limited exploration, increased anxiety, and reduced sociability in the model group. These results suggest alterations in m-GABAA Rβ3 levels, KCC2 levels, and trafficking of GABAA Rs in rats prenatally exposed to valproic acid and advance our understanding of the pathogenesis of ASD.