Inflammatory response in epilepsy is mediated by glial cell gap junction pathway (Review)

Mol Med Rep. 2021 Jul;24(1):493. doi: 10.3892/mmr.2021.12132. Epub 2021 May 6.

Abstract

Epilepsy is a common neurological disease that affects more than 50 million people worldwide. Neuro-inflammation plays an important role in epilepsy. Activation of the immune system and an excessive inflammatory response can increase the frequency of seizures and increase the susceptibility to epilepsy. Therefore, anti-inflammatory therapies may have antiepileptic effects. Connexin 43 (Cx43) is a major component of astroglial hemichannels and gap junctions. Gap junctions are important for the direct exchange of substances and information between cells, as well as regulating the neuroinflammatory response, changing neuronal excitability, neuronal apoptosis, and synaptic remodeling. Cx43-mediated gap junction pathway can be crucial in epilepsy-induced neuroinflammatory cascades. Further, pro-inflammatory cytokines may in turn directly affect the expression of the Cx43 protein in astrocytes. Therefore, examining the association between neuroinflammation and epilepsy can be instrumental in uncovering the pathogenesis of epilepsy, which can lead to the development of novel and more effective antiepileptic drugs.

Keywords: Cx43; epilepsy; neuroinflammation.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Astrocytes / metabolism
  • Central Nervous System / metabolism
  • Connexin 43 / metabolism
  • Epilepsy / etiology*
  • Epilepsy / metabolism*
  • Gap Junctions / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Neuroglia / metabolism*

Substances

  • Connexin 43
  • Adenosine Triphosphate

Grants and funding

This study was funded by the National Natural Science Foundation of China (grant nos. 81801284, 81771396 and 31371125) and Jilin Provincial Ring-fenced Funding for Industrial Innovation Project (grant no. 2017C029-1).