Stymulacja magnetyczna niskiej częstotliwości 1 Hz zmniejsza epilepsję poprzez hamowanie zależnego od interferonu-gamma usuwania synaps przez komórki mikrogleju u myszy

AIMS: We aim to investigate the impact of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on activated microglia in temporal lobe epilepsy (TLE), which exacerbate seizures and memory problems, and to explore the molecular mechanisms and clinical potential of LF-rTMS for TLE treatment. METHODS: We tested 0.3, 0.5, 1 Hz LF-rTMS in kainic acid (KA)-induced TLE mice, assessing EEG, inflammation, synaptic phagocytosis, memory, scRNA-seq, and IFN-γ neutralizing antibodies. SnRNA-seq of human hippocampal sclerosis (HS) tissues confirmed relevance. RESULTS: In KA-induced TLE mice, 1 Hz LF-rTMS decreased seizures, neuroinflammation, and hippocampal synaptic phagocytosis, while enhancing memory. These effects were linked to increased microglial IFN-γ signaling (activating STAT2 and inhibiting CADM1/2/3), which were negated by IFN-γ blockade. SnRNA-seq of human HS tissues revealed elevated IFN-γ signaling in DAM-like cells, indicating clinical relevance. CONCLUSION: Our study indicates that 1 Hz LF-rTMS is a promising treatment for TLE, potentially reducing seizures and cognitive issues by affecting microglial function. Our findings show that IFN-γ signaling triggers STAT2 activation, which is strongly linked to the increased expression of IFN-γ signature DAM and the decreased expression of CADM1/2/3 in DAM, thus playing a role in the neuroprotective effects of 1 Hz LF-rTMS. These findings reveal a new LF-rTMS mechanism and offer insights for targeted therapies in drug-resistant epilepsy.