The Effect Of Overtraining On The Expression Level Of Brain-specific MicroRNAs In The Hippocampus Of Mice

Research objective: The imbalance between exercise load and recovery time may lead to overtraining.This experiment is to explore the effect of overtraining on the cognitive ability of mice and the changes of related brain-derived micro RNAs(miRNAs)in the hippocampus.Verify the dynamic expression pattern between miR-34 a and brain-derived neurotrophic factor(BDNF),its receptor tyrosine kinase B(Trk B)and p75 neurotrophin receptor(p75).Research method: Ninety 8-week-old male C57BL/6J mice were selected and randomly divided into control(CON),aerobic training(NT)and overtraining(OT)groups.After training,the incremental load test(ILT)and the rotating rod test were used to evaluate the exercise performance;the Morris water maze test and the open field test were used to evaluate the cognitive ability of the mice.After48 hours of training and evaluation,the mouse hippocampal tissue was taken,and RT-q PCR was used to detect the expression of miR-34 a,miR-21,miR-124 and miR-132 in the hippocampus;Western Blot was used to detect the expression of BDNF,Trk B,and p75 in the tissue Protein expression and Trk B phosphorylation level.In vitro experiments verified that BDNF is a potential target of miR-34 a,and explored the effect of overexpression of miR-34 a on BDNF and its receptors Trk B and p75.Research results: Both NT and OT significantly decreased their body weight after 8 weeks of training;the results of ILT test and rotating rod experiment showed that OT performance decreased and NT increased significantly.The Morris water maze test showed that NT’s space exploration and location memory abilities were significantly better than those of CON and OT;the open field experiment showed that OT has obvious anxiety tendency.The expression of miR-34 a in the hippocampus of OT mice increased significantly,and the expression of BDNF protein decreased,and the two showed a moderate negative correlation.Overexpression of miR-34 a in vitro can reduce the expression of BDNF and its receptor Trk B,while the expression of p75 protein increases;miR-34 a directly complements and binds to the 3’UTR of BDNF m RNA.BDNF and Trk B protein in the hippocampus of NT mice increased significantly;while the phosphorylation level of p75 protein and Trk B in OT was significantly higher than that of NT and CON.Conclusion: Aerobic training can improve the cognitive ability of mice.Overtraining fails to improve the cognitive ability of mice,but it shows obvious anxiety tendency.After training,the expression of miR-34 a in the hippocampus of OT mice increased,and the expression of BDNF protein decreased significantly.Statistics showed that the two were moderately negatively correlated.Through bioinformatics prediction and in vitro experimental verification,it is found that miR-34 a targets to reduce the expression of BDNF in the hippocampus,and reduces the expression of its receptor protein Trk B,but promotes the protein expression of p75,thereby mediating cognitive changes.