Reduced protein expressions of cytomembrane GABA(A)R beta 3 at different postnatal developmental stages of rats exposed prenatally to valproic acid

摘要

Decreased inhibition plays an extremely important role in pathogenesis of autism spectrum disorder (ASD). Therefore, we aimed to determine whether expression levels of the gamma-aminobutyric acid type A receptor beta 3 subunit (GABA(A)R beta 3), 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 GABA(A)R beta 3 (m-GABA(A)R beta 3) and KCC2 as well as increased endocytosis of GABA(A)Rs were found in the model group. However, there were no significant differences in expression of total GABA(A)R beta 3 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-GABA(A)R beta 3 levels, KCC2 levels, and trafficking of GABA(A)Rs in rats prenatally exposed to valproic acid and advance our understanding of the pathogenesis of ASD. (C) 2017 Elsevier B.V. All rights reserved.