The Mechanism Research About BDNF/TrkB Of MPFC In CUMS Rat With The Intervention Of Electroacupuncture Combined With Paroxetine

BackgroundIn the current study,we observed the effects of electroacupuncture(EA)combined with paroxetine(PA)in chronic unpredictable mild stress(CUMS)and the probable mechanism associated with the brain-derived neurotrophic factor(BDNF)/the tyrosine kinase receptor(TrkB)signaling in the medial prefrontal cortex(mPFC).MethodsThe CUMS method was selected to induce depressive-like behavior in rats.The male adult Sprague Dawley(SD)rats were randomized to the normal control(NC)group and the model group.After successful molding,the model group were randomized four experimental groups,including the CUMS group,the EA group,the PA group,and the EA with PA group.Weight,sucrose preference test(SPT),and open field test(OFT)were assessed.Hematoxylin and eosin(HE)staining,quantitative real-time PCR(qPCR)reaction,and western blotting(WB)were used to detect the changes in the BDNF/TrkB signaling after different interventions.Results(1)The rats in the model group had reduction of weight,SPT,central area residence time and total activity distance compared with NC group(P<0.05).After 2-week intervention,compared with the CUMS group,the above behavioral indexes of other experimental groups all increased significantly(P<0.05).(2)HE staining was used to observe that the EA with PA can reverse the degeneration of neurons in the mPFC,and improve pathological changes such as cell body swelling,vacuoles,nuclear pyknosis,widening of intercellular space,and inflammatory cell infiltration.(3)qPCR was used to observe that the expressions of BDNF mRNA and TrkB mRNA in the mPFC of the rats after CUMS modeling were lower than those in the NC group(P<0.05).After 2-week intervention,compared with the CUMS group,the expressions of BDNF mRNA and TrkB mRNA in the mPFC of rats in the EA with PA group were increased(P<0.05).(4)WB was used to observe that the expression levels of BDNF,pTrkB,and GluN1 proteins in the mPFC of the rats after CUMS modeling were significantly lower than those in the NC group(P<0.05).After 2-week intervention,compared with the CUMS group,the expression level of BDNF protein in the mPFC of rats in the EA with PA group was significantly increased(P<0.05),the expression level of pTrkB protein in the mPFC of rats in PA group and the EA with PA group was significantly increased(P<0.05),the expression level of GluN1 protein in the mPFC of rats in three experimental groups was significantly increased(P<0.05).ConclusionEA with PA improved depressive behavior in CUMS rats,probably by improving the degeneration of mPFC neurons.EA with PA might increase the expression of BDNF/TrkB by increasing the level of GluN1 in mPFC neurons of CUMS rats,finally exerting antidepressant effects.