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Type I interferon signaling promotes kainic acid-induced seizures through mTOR activation

Authors
 Jeong-Hwa Ma  ;  Jun-Cheol Eo  ;  Changjun Lee  ;  Jihye Choi  ;  Inhwa Hwang  ;  Yun-Jeong Yang  ;  Sung Jae Shin  ;  Chul Hoon Kim  ;  Je-Wook Yu 
Citation
 NEUROPHARMACOLOGY, Vol.279 : 110634, 2025-11 
Journal Title
NEUROPHARMACOLOGY
ISSN
 0028-3908 
Issue Date
2025-11
MeSH
1
Keywords
Animals ; Interferon Type I* / metabolism ; Interferon-beta ; Kainic Acid* / toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons / drug effects ; Neurons / metabolism ; Receptor, Interferon alpha-beta / deficiency ; Receptor, Interferon alpha-beta / genetics ; Receptor, Interferon alpha-beta / metabolism ; Seizures* / chemically induced ; Seizures* / metabolism ; Signal Transduction* / drug effects ; Signal Transduction* / physiology ; TOR Serine-Threonine Kinases* / metabolism
Abstract
Epilepsy ; Seizure; Type I interferon ; mTOR
Article Number
 10.1016/j.neuropharm.2025.110634 
DOI
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, yet the role of type I interferon (IFN) signaling in seizure pathogenesis remains elusive. In this study, we show that deficiency of type I IFN signaling reduces seizure severity in a kainic acid-induced mouse model. Ifnar1-/- mice exhibited significantly lower seizure scores at multiple time points (e.g., U = 88.5, p = 0.0078 at 110 min), along with decreased neuronal excitability and microglial activation in these mice in response to kainic acid stimulation. Conversely, intracerebroventricular injection of IFN-β exacerbated kainic acid-induced seizure severity. In vitro calcium imaging demonstrated that IFN-β treatment enhanced neuronal excitability, although no significant difference in basal neuronal excitability were observed between wild-type and Ifnar1-/- neurons. Additionally, Ifnar1-/- mice showed reduced activation of the mammalian target of rapamycin (mTOR) pathway in the brain following kainic acid administration-a pathway known to contribute to epileptogenesis. Consistent with this finding, IFN-β treatment increased mTOR activation, as indicated by S6 phosphorylation in in vitro mixed glial cultures. Taken together, these findings highlight a critical role of type I IFN signaling in seizure progression, potentially via mTOR modulation, and suggest that targeting type I IFNs may offer a promising therapeutic strategy for epilepsy.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/207512
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