Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation (rTMS)_EX_VIVO

Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used in the study and treatment of neurological conditions including major depression, stroke, epilepsy, schizophrenia, multiple sclerosis, Parkinson’s, and Alzheimer’s disease, as well as other, non-neurological disorders. Among the effects of rTMS, low-frequency protocols (≤ 1Hz) are generally understood to result in cortical inhibition, whereas high-frequency protocols (≥ 3Hz) increase cortical excitability. However, the complex molecular basis of rTMS is largely unexplored. Using three complementary rat models, in vitro, ex vivo, and in vivo, we show complex patterns of hippocampal and neocortical transcriptional response to stimulation in glutamatergic and GABAergic signaling pathways, as well as multiple inflammatory pathways, among others. This broad-based molecular survey helps provide a foundation to tease out the complex molecular mechanisms of the effects of rTMS.经颅磁刺激（Transcranial Magnetic Stimulation, TMS）是一种利用脉冲磁场作用于大脑及中枢神经系统生理活动的非侵入性技术。重复经颅磁刺激（Repetitive TMS, rTMS）已被应用于多种神经系统疾病的研究与治疗，包括重性抑郁症、脑卒中、癫痫、精神分裂症、多发性硬化、帕金森病、阿尔茨海默病，以及其他非神经系统病症。在重复经颅磁刺激的各类效应中，低频刺激方案（≤1Hz）通常被认为可诱导皮层抑制，而高频刺激方案（≥3Hz）则能提升皮层兴奋性。然而，重复经颅磁刺激的复杂分子基础目前仍未得到充分探索。本研究采用三种互补的大鼠模型（体外、离体与体内模型），揭示了刺激后海马与新皮层在谷氨酸能、γ-氨基丁酸能信号通路以及多种炎症通路等通路中的复杂转录应答模式。这项覆盖广泛的分子层面研究，为阐明重复经颅磁刺激效应背后的复杂分子机制奠定了基础。