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1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice.

Overview

Authors: Donghui Lin1, Duan Wang2, Nong Xiao1
ORCID iDs: Donghui Lin
  1. Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, China
  2. Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian province, China
Journal: CNS neuroscience & therapeutics, volume 32, issue 6, article e70979
Dates: received 8 February 2026; accepted 30 May 2026; published online 13 June 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/cns.70979 · PMID 42287127 · PMCID PMC13263791 · OpenAlex W7164681993
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), other (modality), human (organism), mouse (organism), epilepsy (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, Machine learning, Spectral & time-frequency
Keywords: epilepsy, microglia, neuroinflammation, repetitive transcranial magnetic stimulation, Type II interferon
MeSH: Epilepsy, Temporal Lobe*, Interferon-gamma*, Microglia*, Phagocytosis*, Synapses*, Transcranial Magnetic Stimulation*, Animals, Humans, Kainic Acid, Male, Mice, Mice, Inbred C57BL, Signal Transduction (* major topic)
Topic: Transcranial Magnetic Stimulation Studies (Neurology, Neuroscience), according to OpenAlex
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 13 MeSH terms, 57 references.

Cite

This paper

Lin, D., Wang, D., & Xiao, N. (2026). 1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice. CNS neuroscience & therapeutics, 32(6), e70979. https://doi.org/10.1002/cns.70979

BibTeX

@article{lin20261,
author = {Lin, Donghui and Wang, Duan and Xiao, Nong},
title = {{1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice}},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = jun,
volume = {32},
number = {6},
pages = {e70979},
publisher = {Wiley},
issn = {1755-5930},
doi = {10.1002/cns.70979},
url = {https://doi.org/10.1002/cns.70979},
pmid = {42287127},
pmcid = {PMC13263791}
}

RIS

TY - JOUR
AU - Lin, Donghui
AU - Wang, Duan
AU - Xiao, Nong
TI - 1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice
T2 - CNS neuroscience & therapeutics
J2 - CNS Neurosci Ther
PY - 2026
DA - 2026/06/01
VL - 32
IS - 6
SP - e70979
SN - 1755-5930
PB - Wiley
DO - 10.1002/cns.70979
UR - https://doi.org/10.1002/cns.70979
LA - en
ER -

CSL-JSON

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