The DNA repair protein ATM as a target in autism spectrum disorder

Impairment of the GABAergic system has been reported in epilepsy, autism, attention deficit hyperactivity disorder, and schizophrenia. We recently demonstrated that ataxia telangiectasia mutated (ATM) directly shapes development system. Here, we show for first time to our knowledge how abnormal expression ATM affects pathological condition autism. exploited 2 different animal models methyl CpG binding protein 2–null (Mecp2y/–) mouse model Rett syndrome mice prenatally exposed valproic acid, found increased levels. Accordingly, treatment with specific kinase inhibitor KU55933 (KU) normalized molecular, functional, behavioral defects these models, such as (a) delayed development, (b) hippocampal hyperexcitability, (c) low cognitive performances, (d) social impairments. Mechanistically, demonstrate KU administration WT neurons leads higher early growth response 4 activity on Kcc2b promoter, Mecp2, potentiated GABA transmission. These results provide evidence molecular substrates pharmacological inhibition autism spectrum disorders.