Abnormal Expression Of M-GABA_AR?3 At Different Postnatal Developmental Stages Of Rats Exposed Prenatally To Valproic Acid

Background:Autism spectrum disorder is a general developmental disorder characterized by social communication deficits,repetitive behavior,and restricted interests.Although the neurobiological basis of ASD is not clear,evidence suggests that Increased excitation/inhibition plays an extremely important role in pathogenesis of autism spectrum disorder(ASD).Objective:we aimed to determine whether expression levels of the ?-aminobutyric acid type A receptor(GABA_AR),K+-Cl-cotransporter 2(KCC2),and Na+-K+-Cl-cotransporter 1(NKCC1)related to inhibition transmission change in a sodium valproate-induced rat model of ASD.Method:For behavior testing,we evaluated developmental landmarks and reflexes as well as performance in open-field,Morris water maze and 3-chamber tests by two investigators blind to group assignment.Expression of total GABA_AR?3,m-GABA_AR?3,p-GABA_AR?3,NKCC1,and KCC2 in different brain regions including the TPC,PRC,HC,and CBC was determined by Western blot assays.Result: Decreased expression levels of membrane GABA_AR?3(m-GABA_AR?3),KCC2 as well as increased endocytosis of GABA_ARs were found in the model group.However,there were no significant differences between control and model groups in expression of total GABA_AR?3 and NKCC1.In addition,we observed growth retardation,impaired spatial memory,limited exploration,and reduced sociability in the model group.Conclusion: These results suggest alternations in m-GABA_AR?3 levels,KCC2 levels,and trafficking of GABA_ARs in rats prenatally exposed to valproate and advance our understanding of the biological mechanism of increased excitation/inhibition in ASD.