| Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on theimprovement of ethology in chronic unpredictable mild stress (CUMS) rats and its relatedmechanism (including the level changes of BDNF (brain derived neurotrophic factor,BDNF), Interleukin-1beta (IL-1β) and Nuclear factor-κB (NF-κB) and the apoptosis andneurogenesis of hippocampal cells).Methods:1.48male SD rats were randomly divided into6groups: sham group, sham+rTMSgroup, CUMS group, CUMS+rTMS group, CUMS+Sertraline group, CUMS+rTMS+Sertraline group (n=8per group). After4weeks of the establishment of CUMS model, rats were received Sertraline (20mg/kg i.g.) and/or rTMS treatment for7days. Immediately after CUMS and after drug administration, rats were subjected tosucrose preference testing, force swimming test and open field test. At the end of thelast behavioral test, the level of IL-1β was detected by Elisa, and the expression ofNF-κB and BDNF were determined by Western blot respectively.2.30male SD rats were randomly divided into5groups: sham group, sham+rTMSgroup, CUMS group, CUMS+rTMS group, CUMS+rTMS+U0126group (n=6pergroup). After4weeks of the establishment of CUMS model, rats were received rTMStreatment for7days. CUMS+rTMS+U0126group were treated with MAPKinhibitors (U0126for extracellular signal-regulated kinase) before rTMS treatment.Immediately after CUMS and after rTMS administration, rats were subjected to forceswimming test and open field test.3rats of each group were sacrificed to obeserve theexpression of BDNF, NF-κB, iNOS, ERK and pERK in hippocampus by Western blotat the end of the last behavioral test. The rest animals were anaesthetized and receivedcitromint heart filling, and the brains were taken for the preparation of hippocampalfrozen sections for staining Neun, DCX and caspase3.Results:1. Effects of rTMS on ethology in CUMS model rats.There was a significant difference among sham group and CUMS group in the freezingtime of force swimming test, the sucrose consumption test and times in center and sniffingon center of open field test (P <0.05). rTMS treatment and rTMS+Sertraline treatmentblocked the reduction of sucrose preference and the times in center and sniffing on centerof chronic unpredictable stress (P <0.05). They also decreased the floating time in forceswimming test of CUMS rats. And these effects were blocked by U0126.2. Effects of rTMS on the level of IL-1β, BDNF, NF-κB, iNOS, ERK, pERK, and theexpression of DCX and caspase3in hippocampus of CUMS rats.Exposure to CUMS resulted in a significant decrease in the expression of pERK andBDNF of hippocampus, and rTMS group showed significantly increase for the expressionof pERK and BDNF than sham group (P <0.05). Increase in the expression of IL-1β,-7- NF-κB and iNOS were also found in hippocampus of CUMS group, and rTMS treatmentblocked the growth of NF-κB and iNOS (P <0.05). There were no difference on theexpression of ERK among groups. The number of cells co-labeled with NeuN, a marker ofneurons, and DCX in the hippocampal DG was also significantly higher in the CUMS+rTMS group and sham group compared with CUMS group (P <0.05). The number ofcaspase3+cells in CUMS group was significantly higher than sham group and CUMS+rTMS group, Furthermore, U0126treatment reserved these changes (P <0.05).Conclusion:The level of IL-1β, NF-κB and iNOS were increased in CUMS rats, and rTMStreatment could relieve the increase and improve animal behaviors. There were no effectson the level of IL-1β, NF-κB and iNOS of normal rats due to rTMS. Combined treatmentof rTMS and Sertraline was more effective. rTMS treatment could mediate cell growth,neurogenesis and apoptosis in hippocampus, exert its neurogenesis effect. Theseimprovements of rTMS could be blocked by U0126. It suggest that the anti-inflammationeffect of rTMS may play an important role in depression therapy, and this effect might bemediated by BDNF and pERK1/2up-regulation. |
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