重复经颅磁刺激对抑郁大鼠学习记忆及海马CA3区超微结构的影响

The influence of repetitive transcranial magnetic stimulation on learning, memory and the ultrastructure of the CA3 region of the hippocampus

目的 观察重复经颅磁刺激（rTMS）对抑郁模型大鼠学习记忆功能及海马CA3区神经元、突触超微结构的影响.方法 采用随机数字表法将40只SD大鼠分为正常对照组（简称对照组）、抑郁模型组（简称抑郁组）、重复经颅磁刺激组（简称rTMS组）及伪刺激组,后3组大鼠采用孤养结合慢性不可预见轻度应激方法制成抑郁大鼠模型,采用蔗糖水消耗实验、Open-field测试评定造模是否成功.待制模成功后,rTMS组大鼠给予为期21 d的rTMS（频率为15 Hz）治疗,伪刺激组则给予相应伪刺激干预.于制模前、制模后及rTMS治疗21d后采用Morris水迷宫定位航行试验及空间探索试验分别评定各组大鼠学习记忆功能;于rTMS治疗21 d后采用透射电子显微镜观察各组大鼠海马CA3区神经元、突触超微结构及各突触参数变化情况.结果 与制模前比较,制模后大鼠在蔗糖水消耗量、Open-field测试-水平运动距离、竖立次数等方面差异均具有统计学意义（P＜0.05）;治疗后rTMS组Morris水迷宫定位航行试验逃避潜伏期[（13.14±2.49）s]、空间探索时间[（65.46±2.39）s]与抑郁组、伪刺激组间差异均具有统计学意义（P＜0.05）,而抑郁组上述指标与伪刺激组间差异均无统计学意义（P＞0.05）;通过电镜观察发现,抑郁组大鼠海马CA3区神经元及突触超微结构均存在病理改变,rTMS组大鼠经治疗后其神经元及突触超微结构均基本趋于正常.结论 rTMS干预对抑郁大鼠学习记忆障碍具有改善作用,其治疗机制可能与rTMS诱发抑郁大鼠海马CA3区神经元及突触结构改变有关.

Objective To investigate the effect of repetitive transcranial stimulation （rTMS） on learning and memory and on the neuron and synapse ultrastructures of the CA3 region of the hippocampus.Methods Forty Sprague-Dawley （SD） rats were randomly divided into 4 groups （n =l0 in each group）：a normal control group,a depression group,an rTMS group and a sham group.Unpredictable mild stress was used to establish depression models in the rats of the latter3 groups.The sucrose water consumption test and open-field test were used to evaluate any depressive behavior of each group.The rTMS group rats were given 15 Hz rTMS for 21 days while the sham group received sham stimulation.The orientational navigation and spatial probe tests were performed on each group using a Morris water maze to evaluate their learning and memory abilities.In addition,changes in the ultrastructure of the CA3 region of the hippocampus were detected using transmission electron microscopy.Results The modelling induced significant differences in the sucrose water consumption test results and in horizontal and vertical behavior in the open-field tests.Escape latency and spatial probe time were significantly different between the rTMS group and the sham and depression groups.There was no significant difference in the behavioral indexes between the depression group and the sham group.Electron microscopy showed pathological changes in the ultrastructures of the neurons and synapses in the CA3 region of the hippocampus among the depression group,while in the rTMS group those ultrastructures tended to be basically normal.Conclusion rTMS can improve learning and memory during depression,at least in rats.A possible mechanism is that rTMS can induce changes in the ultrastructures of neurons and synapses in the CA3 region of the hippocampus.