Effects of electroacupuncture on mice with depression after methamphetamine withdrawal by regulating the hippocampal aquaporin 4 and the BDNF/TrkB/CREB signaling pathway
Objective To observe the effects of electroacupuncture(EA)on hippocampal aquaporin 4(AQP4)and brain-derived neurotrophic factor(BDNF)/tyrosine protein kinase B(TrkB)/cyclic adenosine phosphos effter-element binding protein(CREB)signaling pathways in mice with depression after methamphetamine(MTHE)withdrawal,and to explore the mechanism.Methods Healthy male C57BL/6J mice were randomly divided into blank group,model group and EA group,with 10 mice in each group.The MTHE addiction model in mice of model group and EA group was created by the conditioned place preference test(CPP),and the depression after MTHE withdrawal model in mice was created by a natural withdrawal of MTHE.Mice in blank group and model group did not receive any interventions.EA was performed at Baihui(GV20)and Dazhui(DU14)using a continuous wave at the frequency of 2Hz.The intervention of EA was performed for 15min daily,for 28 consecutive days.Forced swim test(FST)and open field test(OFT)were performed after interventions.Western blot was used to detect the protein expressions of AQP4,BDNF,TrkB,CREB and p-CREB in the hippocampus of mice.Immunofluorescence staining was used to detect the positive expression of AQP4 in the hippocampus of mice.Real-time quantitative PCR was used to detect the mRNA expression of AQP4 in the hippocampus of mice.Results After molding,the CPP value was significantly higher in model group and EA group than that of blank group(both P<0.01),and no significant difference was detected between the former two groups.After MTHE withdrawal,mice in the model group and EA group had significantly longer time from placement in the water to immobility/floating and shorter time spent in the central zone than those of blank group(both P<0.01),and no significant difference was detected between the former two groups.After intervention,mice in the model group had significantly longer time from placement in the water to immobility/floating and shorter time spent in the central zone than those of blank group(both P<0.01).Compared with those of model group,mice in the EA group had significantly shorter time from placement in the water to immobility/floating and longer time spent in the central zone than those of blank group(both P<0.01).After intervention,compared with those of blank group,protein expressions of AQP4,BDNF,TrkB,CREB and p-CREB were significantly lower in mice of model group and EA group(all P<0.01),and they were significantly higher in the EA group than model group(all P<0.01).After intervention,the positive expression of AQP4 was significantly lower in the model group and EA group than blank group(P<0.01),and it was significantly higher in the EA group than that of model group(P<0.01).After intervention,the mRNA level of AQP4 was significantly lower in the model group and EA group than that of blank group(P<0.01),and it was significantly higher in the EA group than that of model group(P<0.01).Conclusion EA can relieve the depression-like behavior of mice after METH withdrawal by regulating AQP4 and the BDNF/TrkB/CREB signaling pathway.
electroacupuncturedepression after methamphetamine withdrawalhippocampusaquaporin 4brain-derived neurotrophic factor(BDNF)/tyrosine protein kinase B(TrkB)/cyclic adenosine phosphos effter-element binding protein(CREB)signaling pathway
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