2. Academic Validation
  3. Cx47 Phosphorylation Exacerbates White Matter Damage and Kainic Acid Induced Epilepsy

Cx47 Phosphorylation Exacerbates White Matter Damage and Kainic Acid Induced Epilepsy

  • CNS Neurosci Ther. 2025 Nov;31(11):e70672. doi: 10.1111/cns.70672.
Yi Li 1 2 3,  Haohan Lin 1 2,  Jiayu Liu 1 2,  Jie Chen 1 2,  Kaifeng Shen 4,  Ningning Chen 1 2,  Songyang Xiang 1 2,  Duan Wang 1 2,  Nong Xiao 1 2,  Tingsong Li 1 2
Affiliations

Affiliations

  • 1 Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
  • 2 Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, China.
  • 3 Department of Neurology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.
  • 4 Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
PMID: 41299860 DOI: 10.1111/cns.70672
Abstract

Aims: Growing evidence implicates dysfunctional myelin in the pathogenesis of temporal lobe epilepsy (TLE). Connexin 47 (Cx47), an oligodendrocytic Gap Junction Protein, maintains myelin integrity. This study investigates the role of Cx47 in myelin impairment and seizure progression in TLE.

Methods: Cx47 and phosphorylated Cx47 (p-Cx47) expression was analyzed in human and mouse TLE brain tissues via Western blot and immunofluorescence. Candidate Cx47 phosphorylation kinases revealed by single-cell RNA Sequencing were validated through immunofluorescence, protein docking, and co-immunoprecipitation. TLE mice were treated with the CaMKII inhibitor KN93 to evaluate its effects on demyelination and seizure burden.

Results: In a experimental mouse model, phosphorylated Cx47 (p-Cx47) was significantly upregulated, recapitulating a similar trend observed in human TLE tissues. This upregulation was accompanied by marked demyelination in the TLE Animals. In mice, increased levels of Cx47 and p-Cx47 were associated with elevated CaMKII and phosphorylated CaMKII (p-CaMKII). The interaction between Cx47 and CaMKII was further confirmed. Moreover, administration of KN93 suppressed the upregulation of Cx47 and p-Cx47, thereby mitigating demyelination and reducing seizure progression.

Conclusions: CaMKII-mediated Cx47 expression and phosphorylation promote demyelination and seizure progression in TLE. Targeting Cx47 phosphorylation may offer a therapeutic strategy for TLE.

Keywords

CaMKII; Cx47; epilepsy; oligodendrocyte; phosphorylation.

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  • Cat. No.
    Product Name
    Description
    Target
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  • HY-15465
    99.42%, CaMK II Inhibitor‎
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