Sema3G/Nrp2信号通路调控海马突触可塑性在运动训练改善脑卒中后认知障碍中的作用机制

Post-stroke cognitive impairment (PSCI) has proved closely related to the hippocampal injury and synaptic plasticity is a major foundation for hippocampal repair. It is demonstrated that physical exercise may improve PSCI, but the underlying mechanism remains unclear. Recent research has shown that Sema3G/Nrp2 signaling pathway is involved in regulating synaptic plasticity in hippocampus. Our previous study suggested that physical exercise may improve the cognitive impairment of chronic cerebral ischemia by promoting the expression of synaptic plasticity-related proteins in hippocampus. Our preliminary experiment indicated that physical exercise increased the content of Sema3G in hippocampus, promoted the activation of silent synapses and alleviated the memory impairment in mice with cerebral infarction. Therefore, we hypothesize that physical exercise could enhance hippocampal synaptic plasticity via Sema3G/Nrp2 signaling pathway, thereby improving PSCI. The cerebral infarction model in mice is established by transient middle cerebral artery occlusion in this research. The two-photon imaging in vivo, brain slice patch-clamp, molecular biology and other methods are adopted to explore whether physical exercise may improve PSCI through strengthening hippocampal synaptic plasticity via Sema3G/Nrp2 signaling pathway. The findings will provide theoretical basis and experimental evidence for further clarifying the mechanism of physical exercise-induced improvement of PSCI and optimizing its rehabilitation strategies.

脑卒中后认知障碍（PSCI）的发生与海马损伤密切相关，而突触可塑性是海马损伤后修复的重要基础。运动训练可改善PSCI，但机制尚未明确。近期研究表明，Sema3G/Nrp2通路参与调控海马的突触可塑性。我们前期的研究发现，运动训练可促进海马内突触可塑性相关蛋白的表达，改善慢性脑缺血所致的认知障碍；预实验提示，运动训练还能增加海马内Sema3G的含量，促进沉默突触的活化，减轻脑梗死小鼠的记忆损害。因此，我们假设，运动训练可能通过激活Sema3G/Nrp2通路，增强海马的突触可塑性，进而改善脑梗死小鼠的认知功能。本研究拟构建tMCAO小鼠模型，采用双光子活体成像、脑片膜片钳及分子生物学等方法，探讨运动训练是否通过增强海马的突触可塑性，改善PSCI，并明确Sema3G/Nrp2通路所起的作用。研究结果可为深入阐明运动训练改善PSCI的作用机制及优化PSCI的康复策略提供理论依据和实验证据。

认知障碍是脑卒中患者常见的临床症状之一，严重影响其日常生活能力及全面的功能康复。运动训练是临床常用的康复治疗手段之一，大量研究表明，运动训练可促进脑卒中后认知障碍的康复，但具体机制尚不明确。本研究通过构建tMCAO小鼠运动训练模型，采用新物体识别实验、巴恩斯迷宫实验等认知行为学评估方法，利用Western blot、尼氏染色及神经电生理等实验技术，探讨运动训练是否通过增强海马突触可塑性，改善脑梗死小鼠的认知功能。本研究发现：运动训练可通过促进海马突触相关蛋白和细胞骨架蛋白的表达，减轻脑梗死小鼠海马神经元的损伤，并能增加海马内信号素Sema3G 的含量，促进沉默突触的活化，显著提高海马CA3-CA1通路场电位的波幅，进而改善脑梗死小鼠的新物体识别能力和空间记忆能力。研究结果表明，运动训练可通过促进海马内信号素Sema3G的表达，增强海马突触可塑性，进而改善脑梗死小鼠的认知功能。研究结果可为深入阐明运动训练改善脑卒中后认知障碍的作用机制及优化其康复策略提供理论依据和实验证据。