Study On The Dynamic Changes Of BDNF TrkB Pathway In The Hippocampus Of The Autism Rat Model Induced By Sodium Valproate

Objective: To investigate the changes in the expression of bdnf-Trk B pathway and the number of neurons in the hippocampus of ASD rat model at different time points,and to explore whether there is an association between these changes,so as to provide an idea for the study of the pathogenesis of autism spectrum disorders.Methods: 24 pregnant rats were randomly injected with VPA(600 mg / kg,250 g / L VPA dissolved in normal saline)in E12.5,and the offspring of pregnant rats were the autistic model rats(model group).Twelve pregnant rats were randomly injected with the same dose of normal saline into the abdominal cavity of E12.5,and the offspring of pregnant rats were taken as the control group.The developmental and behavioral tests were carried out in the two groups.Immunofluorescence and image analysis were used to detect the changes in the number of neurons in the hippocampus of P7,P21,P28,P35 and P42.Western blotting and image analysis were used to detect the changes in the expression of BDNF and Trk B proteins in the hippocampus of P7,P21,P28,P35 and P42.The m RNA expression changes of BDNF and Trk B in hippocampal area of the two groups were detected by fluorescence quantitative PCR at P7,P21,P28,P35 and P42.SPSS26.0 was used for statistical analysis of the data.Results:In this study,compared with the NS group,the following abnormalities were found in the VPA group: 1.developmental and behavioral aspects: weight loss,brain weight increases rapidly in the early stages and slowly in the later stages,delayed time of eye opening,decreased directional tendency ability,increased repetitive behaviors,and decreased learning and memory ability.The above differences were statistically significant(P<0.05).2.Immunofluorescence detection: the number of neurons in the P7,P21,and P28 was more than the control group(P<0.05),and the number of mice neurons in P35?P42was less than the control group(0.05).3.Western blot detection: at P7,P21,and P28,the expressions of BDNF and Trk B proteins in the hippocampus of the VPA group were higher than that of the control group(P<0.05),while at P35 and P42,the expressions of BDNF and Trk B proteins in the hippocampus of the VPA group were lower than that of the control group(P<0.05).4.Fluorescence quantitative PCR detection: at P7,P21,P28,the m RNA expressions of BDNF and Trk B in the hippocampus of the VPA group were both higher than those of the control group(P<0.05),while at P35,P42,the m RNA expressions of BDNF and Trk B in the hippocampus of the VPA group were lower than those of the control group(P<0.05).Conclusion: The BDNF-Trk B pathway in hippocampus of ASD rat model was overexpressed in the early stage and decreased in the later stage.The number of neurons in the hippocampus of ASD mouse model was excessive in the early stage and slow in the later stage.The change in the expression of BDNF-Trk B pathway in hippocampus of ASD rat model was consistent with the change trend of the number of neurons.