Impact of Tongdu Jieyu Acupuncture on BDNF/TrkB/CREB Pathway of Prefrontal Cortex in CUMS Depression Model Rats
Objective:To explore the mechanism of the effect of Tongdu Jieyu acupuncture on the BDNF/TrkB/CREB pathway of prefrontal cortex in chronic unpredictable mild stress(CUMS)depression model rats under the action of K252a.Methods:64 SPF SD rats were randomly divided into the control group,the model group,the Fluoxetine group,the acupuncture group,the model+DMSO group,the model+K252a group,the Fluoxetine+K252a group,and the acupuncture+K252a group,with 8 rats in each group.The depression model was established by CUMS combined with isolation.The acupuncture group and the acupuncture+K252a group were intervened by needling Baihui(DU20)and Shenting(DU24),electro-needling Neiguan(PC6)and Taichong(LR3)for 30 min,continuous wave,frequency of 2 Hz,current of 1mA,at the time of 30 min before modeling;the Fluoxetine group and the Fluoxetine+K252a group were also intervened at 30 min before modeling.The model+DMSO group,the model+K252a group,the Fluoxetine+K252a group and the acupuncture+K252a group were injected with DMSO solution and K252a in the lateral ventricle 1 h before modeling for a total of 21 days.Body mass,sugar and water preference experiment and forced swimming experiment were used to evaluate behavior.The integral optical density(IOD)of BDNF,TrkB and CREB positive cells in the prefrontal cortex of the rats was detected by immunohistochemistry.Western blot and PCR were used to detect the expression of related proteins and mRNA in the prefrontal cortex of the rats.LSD test and non-parametric test were used for statistical analysis.Results:Compared with those in the control group,the body mass difference,sugar and water preference index of SPI,IOD value,and protein and mRNA expressions of BDNF,TrkB and CREB were significantly decreased in the model group(P＜0.01),and the immobility time(IT)in forced swimming was significantly increased in the model group(P＜0.01).Compared with those in the model group,the body mass difference,SPI,IOD,as well as protein and mRNA expressions of BDNF,TrkB and CREB were significantly up-regulated(P＜0.01),and IT was down-regulated in the acupuncture group and the Fluoxetine group(P＜0.01);the body mass,SPI and IOD,as well as protein and mRNA expressions of BDNF,TrkB,CREB were decreased(P＜0.05),and IT was increased in the model+K252a group(P＜0.05).Compared with those in the acupuncture group,the body mass difference,SPI,IOD,as well as protein and mRNA expressions of BDNF,TrkB,CREB were decreased(P＜0.05),and IT was increased in the acupuncture+K252a group(P＜0.05).Conclusion:Tongdu Jieyu acupuncture can significantly improve the depressive behavior of CUMS model rats,and its mechanism may related to up-regulating the BDNF/TrkB/CREB pathway in the prefrontal cortex,so as to play its role in treating depression.
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