低频经颅磁刺激对VCI大鼠学习记忆及海马突触可塑性的影响

发布时间：2018-04-23 06:00

本文选题：学习记忆 + 海马　；参考：《长江大学》2017年硕士论文

【摘要】：背景人口老龄化已成为我国一个非常突出的社会问题。由此带来的各种动脉粥样硬化性疾病(尤其是心脑血管疾病)高发病率已成为严重影响我国老年人群健康的头号问题。脑血管病变引发的卒中患者数量日益增多,卒中除引起运动感觉等功能缺失,很大一部分患者还会遗留有程度不同的认知功能障碍。血管性认知障碍(vascular cognitive impairment,VCI)临床症状表现为学习记忆能力受损的的障碍性疾病,严重者可进展为血管性痴呆。认知障碍造成患者生活自理能力明显下降,给家庭社会带来很大的负担。痴呆已经成为一个越来越严重的全球性公共卫生问题,受到各国神经病学研究人员和政府的重视。目前治疗中仍无特效的药物和治疗手段。如何改善认知功能问题已成为脑科学的重要研究课题。重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)是近年逐渐应用于临床的一种影响和改变大脑功能的磁刺激技术,治疗效果在多种神经精神疾病的治疗中得到了肯定。但在对认知功能障碍的改善上的影响研究相对较少,作用机制不清。认知是人脑特有的高级功能。脑结构中与学习记忆最密切的脑区是海马。中枢神经元的突触可塑性决定着学习记忆功能。长时程增强(long-term potentiation,LTP)现象是中枢神经突触可塑性的重要形式和指标。VCI模型大鼠为实验研究对象,Morris水迷宫进行动物行为学实验,电生理学实验观察海马突触功能可塑性,从宏观和微观两角度观察低频重复经颅磁刺激对VCI大鼠学习和大鼠脑海马区长时程增强现象的影响。目的研究低频重复经颅磁刺激对血管性认知障碍大鼠认知功能的影响,探讨低频经颅磁刺激治疗对血管性认知障碍大鼠的认知影响和细胞水平的分子机制,为磁刺激治疗血管性认知障碍提供理论依据,丰富治疗手段。方法实验动物2个月龄大雄性SD大鼠75只,随机等分为正常组、假手术组、模型组、rTMS刺激组四组(造模成功后每组为15只)。VCI模型大鼠制备采用间断夹闭双侧颈总动脉伴低血压法。Morris水迷宫通过逃避潜伏期和穿越平台次数测试进行动物行为学实验。电生理学实验采用电生理技术记录胞外刺激诱发的海马区群峰电位的变化率为对照指标,并观察海马区突触长时程增强(LTP)形成情况。步骤为制备含海马的大鼠脑片,置于灌流有95%O2+5%CO2混合气体与人工脑脊液的灌流槽内。脑片海马前穿通纤维区放置刺激电极,齿状回放置记录电极,DS3电子刺激器产生诱发电刺激群峰电位显示于示波器上,Spike2数据分析软件分析。以各时间点的群峰电位变化幅值与基础幅值比较所得出的相对百分比(%)作为结果记录并观察LTP形成的现象。统计学分析数据统计分析采用SPSS19.0软件,水迷宫结果及海马突触区群峰电位(PS)变化幅值与基础幅值比较的百分率等计量资料以均数±标准差(?x士s)表示。组间比较采用One way NAOVA分析,P0.05认定结果有统计学意义。结果假手术组大鼠与正常组大鼠比较差异无统计学意义,单纯手术操作不会加重大鼠认知功能障碍。VCI模型大鼠学习记忆能力与正常大鼠比较明显下降。Morris水迷宫实验VCI大鼠定位巡航、穿越平台能力下降,离体存活脑片海马齿状回区LTP减弱。低频rTMS刺激VCI模型大鼠后可改善模型大鼠学习记忆能力,表现为模型大鼠定位巡航实验,空间探索实验能力增强,海马区LTP现象增加。实验中未见实验鼠不良反应,各组大鼠均耐受性良好,低频rTMS治疗安全有效。结论rTMS可能因增强VCI模型大鼠海马区突触的功能可塑性而安全有效地改善VCI模型大鼠的学习记忆认知功能。
[Abstract]:The aging of the population has become a very prominent social problem in China. The high incidence of all kinds of atherosclerotic diseases, especially the cardiovascular and cerebrovascular diseases, has become the first problem that seriously affects the health of the elderly in our country. The number of stroke patients caused by cerebrovascular disease is increasing, and the stroke causes a sense of movement. A large part of the patients will still have a different cognitive impairment. The clinical symptoms of vascular cognitive impairment (VCI) are manifested by impaired learning and memory impairment, and the serious people can develop into a vascular idiot. Cognitive impairment leads to the patient's self-care ability. The decline has brought a great burden to the family society. Dementia has become a more and more serious global public health problem. It has been paid much attention by neurology researchers and government in various countries. There are still no special drugs and treatments in the treatment. How to improve cognitive function has become an important research topic in brain science. Repetitive transcranial magnetic stimulation (rTMS) is a magnetic stimulation technique that has been gradually applied to the clinic in recent years to influence and change the function of the brain. The therapeutic effect has been confirmed in the treatment of many neuropsychiatric disorders. However, the effect on the improvement of cognitive impairment is relatively less and the mechanism of action is relatively less. Not clear. Cognition is a unique advanced function of the human brain. The brain region which is most closely related to learning and memory is the hippocampus. The synaptic plasticity of the central neurons determines the learning and memory function. The long-term potentiation (LTP) phenomenon is an important form and index of the plasticity of the central nervous synapse. The rat model of the.VCI model is the experimental study of the experimental study. Elephant, Morris water maze conducted animal behavior experiments and electrophysiological experiments to observe the plasticity of hippocampal synaptic function. The effects of low-frequency repetitive transcranial magnetic stimulation on the long Shi Cheng enhancement phenomenon in VCI rats and rat hippocampus were observed from the macroscopic and microscopic two angles. Objective to study the effects of low frequency repetitive transcranial magnetic stimulation on vascular cognitive impairment rats The effect of cognitive function on the cognitive effects of low frequency transcranial magnetic stimulation therapy on cognitive impairment in rats and the molecular mechanism of cell level, providing a theoretical basis for the treatment of vascular cognitive impairment by magnetic stimulation, and enriching the treatment methods. Methods 75 rats of 2 months old male SD rats were randomly divided into normal group and sham operation group. Model group, four groups of rTMS stimulation group (15 rats in each group after model success).VCI model rats were prepared by intermittent clamping of the bilateral common carotid artery and hypotension in.Morris water maze. The experiment of animal behavior was carried out by the escape latency and the number of crossing platform times. Electrophysiological experiments used electrophysiological techniques to record the hippocampus induced by extracellular stimulation. The change rate of the peak potential of the region was the control index, and the formation of the synaptic long time potentiation (LTP) in the hippocampus was observed. The step was to prepare the rat brain slices containing the hippocampus in the perfusion slot with 95%O2+5%CO2 mixed gas and artificial cerebrospinal fluid. The stimulation electrode was placed in the anterior hippocampus of the brain slices, the recording electrode was placed in the dentate gyrus, and the DS3 electron was placed. The stimulator generated the generation of generating electricity to stimulate the peak potential of the peak potential on the oscilloscope, Spike2 data analysis software analysis. The relative percentage (%) of the peak potential change amplitude compared with the basic amplitude at each time point is recorded and observed the phenomenon of LTP formation. Statistical analysis of statistical analysis uses SPSS19.0 software, water maze. Results and the percentage of peak potential (PS) changes in the hippocampal synapse region and the percentage of basic amplitude compared with the basic amplitude (? X s). Compared with the One way NAOVA analysis, the results of P0.05 identification were statistically significant. The results showed that there was no statistically significant difference between the rats in the sham operation group and the normal group, and the simple surgical operation was not significant. The ability of learning and memory in.VCI model rats was significantly lower than that of normal rats..Morris water maze test of VCI rats was located on cruise, the ability to cross the platform decreased, and the LTP in the hippocampal dentate gyrus of the isolated surviving brain slices decreased. The low frequency rTMS stimulated the learning and memory ability of the model rats after the stimulation of the VCI model. This is the model rat positioning cruise experiment. The ability of space exploration and experiment is enhanced and the LTP phenomenon in the hippocampus is increased. There is no adverse reaction in the experimental rats. The rats in each group are well tolerated and the low frequency rTMS is safe and effective. Conclusion rTMS may improve the function plasticity of the synapse in the hippocampus of the VCI model rats and improve the VCI model safely and effectively. The cognitive function of learning and memory in rats.

【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.13

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