Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation.
Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation.
复制标题
小胶质细胞因子介导10赫兹重复磁刺激诱导的可塑性。
DOI：
10.1523/jneurosci.2226-22.2023
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发表时间：
2023-04-26
影响因子：
5.3
通讯作者：
Vlachos, Andreasi
中科院分区：
文献类型：
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作者：
Eichler, Amelie;Kleidonas, Dimitrios;Turi, Zsolt;Fliegauf, Maximilian;Kirsch, Matthias;Pfeifer, Dietmar;Masuda, Takahiro;Prinz, Marco;Lenz, Maximilian;Vlachos, Andreasi
小胶质细胞是中枢神经系统的常驻免疫细胞，感知神经元的活动并调节生理性脑功能。它们与神经兴奋性和可塑性改变相关的脑疾病的病理学有关。然而，以脑区域特异性方式调节小胶质细胞功能的实验和治疗方法尚未建立。在这项研究中，我们测试了重复经颅磁刺激（rTMS），一种临床使用的无创脑刺激技术，对小胶质细胞介导的突触可塑性的影响; 10 Hz的电磁刺激触发释放可塑性促进细胞因子的小胶质细胞在小鼠器官型脑组织培养的两种性别，而小胶质细胞形态或小胶质细胞动力学没有显着变化进行观察。事实上，肿瘤坏死因子α（TNFα）和白细胞介素6（IL 6）的替代在小胶质细胞缺失的情况下保留了10 Hz刺激诱导的突触可塑性。与这些研究结果一致，在体内消耗的小胶质细胞废除rTMS诱导的神经传递的变化在mPFC的麻醉小鼠的性别。我们的结论是，rTMS通过调节小胶质细胞释放细胞因子影响神经兴奋性和可塑性。重复经颅磁刺激（rTMS）是一种诱导皮质可塑性的无创脑刺激技术。尽管其在神经科学和临床实践中广泛使用（例如，抑郁症治疗），rTMS介导的可塑性的细胞和分子机制仍然没有得到很好的理解。在此，我们报告了小胶质细胞和可塑性促进细胞因子在器官型切片培养物和麻醉小鼠中由10 Hz rTMS诱导的突触可塑性中的重要作用，从而将小胶质细胞介导的突触适应确定为基于rTMS的干预的靶点。
Microglia, the resident immune cells of the CNS, sense the activity of neurons and regulate physiological brain functions. They have been implicated in the pathology of brain diseases associated with alterations in neural excitability and plasticity. However, experimental and therapeutic approaches that modulate microglia function in a brain region-specific manner have not been established. In this study, we tested for the effects of repetitive transcranial magnetic stimulation (rTMS), a clinically used noninvasive brain stimulation technique, on microglia-mediated synaptic plasticity; 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from microglia in mouse organotypic brain tissue cultures of both sexes, while no significant changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor α (TNFα) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microglia. Consistent with these findings, in vivo depletion of microglia abolished rTMS-induced changes in neurotransmission in the mPFC of anesthetized mice of both sexes. We conclude that rTMS affects neural excitability and plasticity by modulating the release of cytokines from microglia. SIGNIFICANCE STATEMENT Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that induces cortical plasticity. Despite its wide use in neuroscience and clinical practice (e.g., depression treatment), the cellular and molecular mechanisms of rTMS-mediated plasticity remain not well understood. Herein, we report an important role of microglia and plasticity-promoting cytokines in synaptic plasticity induced by 10 Hz rTMS in organotypic slice cultures and anesthetized mice, thereby identifying microglia-mediated synaptic adaptation as a target of rTMS-based interventions.