Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation (rTMS)_EX_VIVO. 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. Overall design: Gene expression microarray analysis of sequential ex vivo hippocampal slices (N=36) from four young (Y), four aged-unimpaired (AU), and four aged-impaired (AI) animals at the one hour time-point after either sham, iTBS or 1Hz transcranial magnetic stimulation (TMS) treatment.

经颅磁刺激（Transcranial Magnetic Stimulation, TMS）是一种非侵入性技术，通过脉冲磁场调控大脑与中枢神经系统的生理状态。重复经颅磁刺激（Repetitive TMS, rTMS）已被广泛应用于多种神经疾病的研究与临床治疗，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系统疾病的相关探索。
在rTMS的诸多生物学效应中，目前学界普遍认为低频刺激方案（≤1Hz）可诱导皮层产生抑制效应，而高频刺激方案（≥3Hz）则会提升皮层兴奋性。然而，rTMS发挥作用的复杂分子基础目前仍未得到充分阐释。
本研究采用体外（in vitro）、离体（ex vivo）与体内（in vivo）三种互补的大鼠模型，揭示了谷氨酸能（glutamatergic）、γ-氨基丁酸能（GABAergic）信号通路以及多种炎症通路等在内的海马与新皮层对刺激的复杂转录反应模式。这项覆盖广泛的分子分析研究，为厘清rTMS效应背后的复杂分子机制奠定了重要基础。
实验设计概要：对4只年轻（Y）、4只老年无损伤（AU）以及4只老年损伤（AI）大鼠的系列离体海马脑片（N=36），分别在接受假刺激、间歇性θ爆发刺激（iTBS）或1Hz经颅磁刺激（TMS）处理1小时后，开展基因表达微阵列分析。