重复经颅磁刺激对慢性应激抑郁大鼠抑郁行为及海马神经元再生的影响

目的 观察重复经颅磁刺激(rTMS)对慢性应激抑郁大鼠抑郁行为及海马神经元再生的影响,并探讨rTMS治疗抑郁症的可能机制.方法 共选取36只雄性SD大鼠,采用随机数字表法将其分为对照组、模型组及rTMS组.采用长期、不可预见性、中等强度应激将模型组及rTMS组大鼠制成抑郁动物模型,对照组大鼠未给予特殊处理.rTMS组于制模成功后给予rTMS治疗.各组大鼠分别于治疗前及治疗2周后采用Open-field试验检测行为学改变;采用免疫组织化学染色法检测海马齿状回区(DG)神经前体细胞标记物-巢蛋白(Nestin)表达,并通过检测5-溴脱氧尿苷(BrdU)水平观察DG区神经前体细胞增殖情况,选用Western blot法检测各组大鼠海马脑源性神经营养因子(BDNF)表达.结果 对照组大鼠DG区存在神经前体细胞,并且其中一些细胞处于分裂增殖状态;与对照组比较,模型组大鼠DG区神经前体细胞数量明显减少,增殖功能明显减弱,同时海马区BDNF表达亦显著降低;与模型组比较,rTMS组行为学评分明显改善,DG区神经前体细胞数量及增殖功能均明显提高,海马区BDNF表达亦显著增强.结论 rTMS能改善抑郁症大鼠抑郁行为,其治疗机制可能与rTMS增强海马BDNF表达,从而提高DG区神经前体细胞数量、促进其增殖有关.

Effects of repetitive transcranial magnetic stimulation on depression behavior and hippocampus neuron regeneration in chronic stress depression rats

Objective To study the effects of repetitive transeranial magnetic stimulation (rTMS) on depression behavior and hippocampus neuron regeneration in rats with chronic stress depression and to explore the therapeutic mechanism of rTMS on depressive disorder.Methods Thirty-sixth rats were divided into a control group, a model group and a rTMS group randomly, with 12 rats in each group.The depression model of rat was established by exerting long-term unpredictable moderate stress on the animals.Rats in rTMS group were given rTMS treatment after stress, while those in the control group were not given rTMS treatment.Open-field test was performed to test depression behavior of rats in each group before and after 2 weeks of rTMS treatment.Immunohistochemistry technique was used to detect expression of nestin, a marker of dentate gyrus (DG) neural precursor cells.Neuron regeneration was observed by use of 5-bromodeoxyuridine(5-BrdU).The expression of brain-derived neurotrophic factor (BDNF) in hippocampus was detected through western blot.Results There observed neural precursor cells in DG area of rats in control group and some of them were proliferating.Compared with control group, the number of DG progenitor cells and proliferating ability of DG progenitor cells decreased in model group.The expression level of BDNF in model group was lower than that in model group as well.After rTMS treatment, depression behavior of rats in rTMS group improved significantly, number of DG progenitor cells increased and proliferating ability of DG progenitor cells elevated significantly.The expression level of BDNF in rTMS group was higher than that in model group as well.Conclusion rTMS therapy could ameliorate depressive behavior of depression rat.The therapeutic mechanism may be associated with rTMS promoting expression of BDNF in hippocampus, which increasing number of neural precursor cells in DG and promoting the proliferation DG neurons as results.