CNS neuroscience & therapeutics · 2026
1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice.
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Lin Donghui, Wang Duan, Xiao Nong
Аннотация
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.
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.