Study On The Mechanism Of Acupuncture At Baihui Point In The Treatment Of Autism Based On BDNF-ERK-CREB Signal Pathway

Objective:The study found that BDNF and BDNF-ERK-CREB signaling pathways are closely related to the pathogenesis of autism.Based on the "kidney marrow brain" theory of traditional Chinese medicine,we believe that acupuncture can regulate BDNF and BDNF-ERK-CREB signal pathway through the "meridian nerve endocrine" network to achieve the effect of treating autism.This study investigated the mechanism of acupuncture at Baihui Point in the treatment of autism by observing the changes of behavior,PSD-95 protein expression in hippocampus and BDNF and CREB m RNA expression in hippocampus of autism model rats after acupuncture at Baihui Point.Methods:The model was made by intraperitoneal injection of valproic acid(VPA)into pregnant rats.Thirty six autistic offspring were divided into acupuncture group,model group and ana-12 group,with 12 in each group;Another 12 normal offspring were taken as the blank control group.The acupuncture group was treated with0.5-inch oblique needling 2mm in front and twirling method.Each time,the needle was kept for 30 min,and the acupuncture was performed once every 15 min.From the p28 d of the offspring,the rats were treated once a day for 21 days;The rats in each group were fed under the same conditions.Then,the behavioral differences of rats in each group were observed by ultrasonic phonation,three box social interaction,bead embedding test,open field test,new object recognition and elevated cross maze test;The expression of PSD-95 protein in hippocampus was observed by immunohistochemistry;The expression of BDNF and CREB m RNA in hippocampus of rats in each group was observed by RT qPCR.Results:(1)compared with the normal group,the experimental rats in autism model group and ANA-12 group had social defects,stereotyped behavior,severe anxiety and impaired learning and memory ability.In addition to learning and memory ability,the symptoms in ANA-12 group were more obvious.Compared with the model group,the experimental rats in acupuncture group had enhanced social ability and reduced stereotyped behavior,The degree of anxiety was mild and the ability of learning and memory increased.The general exploration ability of autism model rats decreased,but there was no significant difference among other groups.(2)Immunohistochemical technique observed that compared with the normal group,the positive expression of PSD-95 in hippocampus of model group and ANA-12 group decreased(P<0.05).Compared with the model group,the positive expression of PSD-95 in hippocampus of acupuncture group increased significantly(P<0.05),while the positive expression of PSD-95 in hippocampus of ANA-12 group decreased((P<0.05).(3)The results of RT-qPCR showed that the relative expression of BDNF and CREB m RNA in hippocampus of model group,acupuncture group and ANA-12 group decreased significantly(P<0.05).Compared with the model group,the expression of BDNF and CREB m RNA in hippocampus of acupuncture group increased(P<0.05),while the expression of BDNF and CREB m RNA in hippocampus of ANA-12 group decreased(P<0.05).Conclusion:(1)this study confirmed that acupuncture at Baihui Point has the effect of treating autism from the behavioral,morphological and molecular levels;(2)According to the experimental results,the correlation between the pathogenesis of autism and BDNF and BDNF-ERK-CREB signal pathway is also clarified.The possible mechanism of acupuncture at Baihui Point in the treatment of autism is to reverse the abnormal expression of PSD-95 protein and BDNF and CREB m RNA in VPA model rats,effectively improve the expression of PSD-95 and BDNF protein and change synaptic plasticity,So as to change the behavior of autistic rats.