Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation (rTMS)_IN_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. Gene expression microarray analysis of 48 mouse brain samples, consisting of matched sets of hippocampus (HIPP, N=24) and parietal cortex (PCTX, N=24) from young sham (Y_Sham, N=4), young iTBS (Y_iTBS, N=4), age-unimpaired sham (AU_Sham, N=4), AU_iTBS (N=5), aged-impaired sham (AI_Sham, N=4) , and AI_iTBS (N=3), obtained 48 hours after either sham or iTBS transcranial magnetic stimulation (rTMS) treatment. TR and TER indicates technical repeats within and between experiments.