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

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）是一种无创技术，通过脉冲磁场调控大脑与中枢神经系统的生理活动。重复经颅磁刺激（Repetitive TMS, rTMS）已被应用于多种神经病症的研究与治疗，涵盖重度抑郁症、脑卒中、癫痫、精神分裂症、多发性硬化、帕金森病与阿尔茨海默病，同时也可用于其他非神经类疾病的相关研究。在重复经颅磁刺激的各类效应中，低频率刺激方案（≤1Hz）通常被认为会引发皮层抑制，而高频率刺激方案（≥3Hz）则会提升皮层兴奋性。然而，重复经颅磁刺激背后复杂的分子机制仍未得到充分探索。本研究采用体外、离体与体内三种互补的大鼠模型，揭示了谷氨酸能与γ-氨基丁酸能信号通路，以及多种炎症通路等在海马体与新皮层中受刺激后产生的复杂转录应答模式。这项覆盖广泛的分子层面调研，为厘清重复经颅磁刺激效应背后的复杂分子机制奠定了研究基础。