Research reportReduced protein expressions of cytomembrane GABAARβ3 at different postnatal developmental stages of rats exposed prenatally to valproic acid

- Abnormal behaviors and protein levels occurred during early stages of growth in rats prenatally exposed to VPA.
- Decreased expression levels of m-GABAARβ3 and KCC2 contributing to reduced inhibition in brain were found in VPA group.
- Prenatal exposure to VPA may increase GABAARs endocytosis which partly explain how m-GABAARβ3 levels were decreased.

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 (GABAARβ3), 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 GABAARβ3 (m-GABAARβ3) and KCC2 as well as increased endocytosis of GABAARs were found in the model group. However, there were no significant differences in expression of total GABAARβ3 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-GABAARβ3 levels, KCC2 levels, and trafficking of GABAARs in rats prenatally exposed to valproic acid and advance our understanding of the pathogenesis of ASD.