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目的:海马突触可塑性降低与脑老化引起的认知功能降低密切相关。已知突触结构功能可塑性是认知的生物学基础,突触蛋白的变化可反映突触结构变化,而突触蛋白上游的调控因子及作用通路不明。经颅磁刺激(TMS)作为无痛、非侵入性的理疗手段,临床可改善神经系统与精神疾病的认知障碍,而基础研究初步证实其与神经重塑相关,但作用机制不明。方法:以15月龄雄性Swiss小鼠为研究对象,实施低频(1Hz)TMS,观察老龄动物空间学习认知行为(Morris水迷宫)、海马突触形态(突触超微结构)、突触蛋白(SYN、GAP43)及上游信号通路(BDNF通路)表达情况。结果:本研究行为学结果表明,TMS可改善老龄小鼠空间学习与记忆能力的损伤;透射电镜(TEM)结果显示TMS可改善老龄小鼠脑海马神经元的生存状态,并影响突触超微结构(增加海马突触密度和PSD平均厚度);分子生物学结果显示,TMS可上调突触蛋白SYN、GAP43免疫阳性产物表达与转录,并激活BDNF-Trk B通路;相关性统计学分析证实BDNF表达转录与认知呈正相关。结论:上述结果提示TMS可能通过BDNF信号通路调节小鼠海马神经元突触蛋白表达、影响突触超微结构、改善认知行为。本研究从海马突触重塑角度揭示TMS改善老龄脑认知能力的作用,从突触形态、突触神经递质传递能效及突触信号转导通路的变化等多层次阐明磁刺激影响可塑性的机制,明确TMS对神经网络重建和再生的作用。
OBJECTIVE: The decrease of hippocampal synaptic plasticity is closely related to the decrease of cognitive function induced by brain aging. Known synaptic plasticity of function is the biological basis of cognition, changes in synaptic protein can reflect changes in synaptic structure, and upstream of the synaptic protein regulatory factors and the role of unknown. Transcranial magnetic stimulation (TMS) as a painless and noninvasive physical therapy can ameliorate the cognitive impairment of the nervous system and mental diseases clinically. However, preliminary studies have shown that TMS is related to nerve remodeling but its mechanism of action is unknown. METHODS: Male Sprague-Dawley (SD) mice at 15 months of age were used as experimental subjects. Low-frequency (1 Hz) TMS was performed to observe spatial cognitive behavior (Morris water maze), synaptic ultrastructure, synaptic (SYN, GAP43) and the upstream signaling pathway (BDNF pathway) expression. Results: The behavioral results of this study showed that TMS can improve the spatial learning and memory impairment of aged mice. Transmission electron microscopy (TEM) results showed that TMS can improve the survival of hippocampal neurons in aged mice and affect the synaptic ultrastructure (Increase of synaptic density and average PSD of hippocampus). The results of molecular biology showed that TMS up-regulated the expression and transcription of SYN and GAP43 immunopositive products of synaptotagmin and activated BDNF-Trk B pathway. The correlation analysis confirmed that BDNF Expression transcription and cognition were positively correlated. Conclusion: The above results suggest that TMS may regulate synaptic protein expression in the hippocampal neurons through the BDNF signaling pathway, which may affect the ultrastructure of synapse and improve cognitive function. In this study, we explored the role of TMS in improving cognitive ability of the aged brain from the perspective of hippocampal synaptic remodeling. The effects of magnetic stimulation on the plasticity were elucidated from the synaptic morphology, the energy transfer efficiency of synaptic neurotransmitters and the changes of synaptic signal transduction pathways Mechanism, a clear TMS neural network reconstruction and regeneration role.