Studies On The Effect Of Autophagy Regulating The P38/MEF2C Pathway To Regulate The Expression Of Synaptic Related Proteins On Improving The Symptoms Of Autism

objective: To investigate the mechanism of p38/MEF2 C pathway regulating synaptic related proteins in autistic rats before and after autophagy intervention.Methods: Wistar rats were used at 12.5 days of gestation,the autism model was induced by intraperitoneal injection of valproic acid(VPA),progeny of valproic acid injection were labeled as model group,intraperitoneal injection of the same amount of saline produced offspring labeled as control,When offspring mice were born at 35 days,30 offspring from pregnant mice treated with VPA were selected and divided into three groups: 10 mice in the autophagy inhibition group(3-methyladenine,3-MA group)were intraperitoneally injected with 3-methyladenine(5mg/kg).in the autophagy enhancement group(Rapamycin,Rap group),10 mice were injected intraperitoneally with Rapamycin(5mg/kg).the remaining 10 were labeled as model group,and another 10 were taken from the control group.both model group and control group received intraperitoneal injection of the same dose of solvent,and each group was treated for one week.The autistic-like behavior changes of rats in each group before and after autophagy intervention were compared by self-grooming experiment and three-box experiment.western blot was used to detect the changes in the expression of p38/MEF2 C pathway related proteins and synaptic related proteins before and after autophagy intervention,and HE staining was used to observe the morphological changes in the prefrontal cortex and hippocampus of each group.Detection of synaptic-related protein expression before and after autophagy intervention by immunohistochemistry.Results: 1.Developmental level assessment: The open eyes experiment showed that the open eyes time in the model group was later than that in the control group(P<0.05).the swimming test showed that the swimming ability of the model group was worse than that of the control group(P<0.05).the negative experiment showed that the rotation turning time of the model group was longer than that of the control group(P<0.05).the behavioral test showed that compared with the control group,the model group showed repeated and stereotyped behaviors and social disorders(P<0.05).compared with the model group,the Rap group improved repetitive and stereotyped behaviors and social disorders(P<0.05),and the 3-MA group increased repetitive and stereotyped behaviors and social disorders(P<0.05).2.Western blot results showed that the expressions of p38,p-p38,MEF2 C,and Gephyrin in the prefrontal cortex of rats in the model group were all down-regulated(P<0.05),while the expressions of SYN and PSD-95 were up-regulated(P<0.05).compared with the control group,the expressions of LC3-II and Gephyrin in the hippocampus of the model group were down-regulated(P<0.05),while the expressions of SYN,PSD-95 and p62 were up-regulated(P<0.05).compared with the model group,the expressions of p38,p-p38,MEF2 C and Gephyrin in the prefrontal cortex of the Rap group were up-regulated(P<0.05),while the expressions of SYN and PSD-95 were down-regulated(P<0.05).compared with the model group,the expressions of LC3-II and Gephyrin in the hippocampus of the Rap group were up-regulated(P<0.05),while the expressions of SYN,PSD-95 and p62 were down-regulated(P<0.05).compared with the model group,the expressions of p38,p-p38,MEF2 C and Gephyrin in the prefrontal cortex of the 3-MA group were down-regulated(P<0.05),and the expressions of SYN and PSD-95 were up-regulated(P<0.05).compared with the model group,the expressions of LC3-II and Gephyrin in the hippocampus of the 3-MA group were down-regulated(P<0.05),while the expressions of SYN,PSD-95 and p62 were up-regulated(P<0.05).3.Immunohistochemistry showed that,compared with the control group,the number of positive cells of SYN and PSD-95 in the prefrontal cortex and hippocampus of the model group increased(P<0.05),while the number of positive cells of Gephyrin decreased(P<0.05).compared with the model group,the number of positive cells of SYN and PSD-95 in the Rap group decreased(P<0.05),and the number of positive cells of Gephyrin increased(P<0.05).the number of positive cells of SYN and PSD-95 in the 3-MA group increased(P<0.05),and the number of positive cells of Gephyrin decreased(P<0.05).Conclusions: 1.Decreased autophagy activity and abnormal expression of synaptic related proteins in autistic rats,2.The p38/MEF2 C pathway is abnormal in autistic rats,and enhanced autophagy can activate the p38/MEF2 C pathway,regulate the expression of synaptic related proteins,and thereby improve the symptoms of autism.