EGCG调节小脑浦肯野细胞兴奋性改善VPA诱导小鼠行为缺陷OA

Objective To investigate the effects of epigallocatechin-3-gallate(EGCG)administration on cerebellar Purkinje cell excitability and inhibitory synaptic activity in valproic acid(VPA)-induced autism spectrum disorder(ASD)mice,as well as its effects on autism-like stereotyped behaviors and motor coordination/balance deficits.Methods A VPA-induced ASD mouse model was established via intraperitoneal injections of EGCG(25 mg/kg and 50 mg/kg).Behavioral tests,including marble burying,self-grooming,accelerating rotarod,and balance beam tests,were used to assess repetitive stereotyped behaviors and motor coordination/balance among four groups:normal control,VPA,VPA+25 mg/kg EGCG,and VPA+50 mg/kg EGCG.Electrophysiological recordings were used to investigate alterations in both excitatory and inhibitory synaptic activity of cerebellar Purkinje cells across these groups.Results In the marble burying and self-grooming tests,50 mg/kg EGCG significantly alleviated repetitive stereotyped behaviors in VPA-induced ASD mice(P＜0.01).In the accelerated rotarod and balance beam tests,50 mg/kg EGCG markedly improved motor coordination and balance abilities in VPA-induced ASD mice(P＜0.01).Whole-cell patch-clamp recordings demonstrated that 50 mg/kg EGCG effectively ameliorated VPA-induced reductions in both cerebellar Purkinje cell excitability(P＜0.05)and inhibitory synaptic activity(P＜0.05,P＜0.01),without affecting excitatory synaptic activity(P＞0.05).Conclusions EGCG dose-dependently modulated the altered excitability and inhibitory synaptic activity of cerebellar Purkinje cells,thereby ameliorating autism-like stereotyped behaviors and motor coordination and balance impairments in VPA-induced ASD mice.