Astrocytes and Glutamine Synthetase in Epileptogenesis. Issue 11 (18th July 2018)

• Record Type: Journal Article
• Authors: Eid, Tore; Lee, Tih‐Shih W.; Patrylo, Peter; Zaveri, Hitten P.
• Other Names: Thippeswamy Thimmasettappa guestEditor.
• Is Part Of: Journal of neuroscience research. Volume 97:Issue 11(2019)
• Page Start: 1345
• Page End: 1362
• Publication Date: 2018-07-18
• Subjects: ammonia -- brain networks -- epilepsy -- excitotoxicity -- glutamate -- inflammation; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24267
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: The cellular, molecular, and metabolic mechanisms that underlie the development of mesial temporal lobe epilepsy are incompletely understood. Here we review the role of astrocytes in epilepsy development (a.k.a. epileptogenesis), particularly astrocyte pathologies related to: aquaporin 4, the inwardly rectifying potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, excitatory amino acid transporters EAAT1 and EAAT2, and glutamine synthetase. We propose that inhibition, dysfunction or loss of astrocytic glutamine synthetase is an important causative factor for some epilepsies, particularly mesial temporal lobe epilepsy and glioblastoma‐associated epilepsy. We postulate that the regulatory mechanisms of glutamine synthetase as well as the downstream effects of glutamine synthetase dysfunction, represent attractive, new targets for antiepileptogenic interventions. Currently, no antiepileptogenic therapies are available for human use. The discovery of such interventions is important as it will fundamentally change the way we approach epilepsy by preventing the disease from ever becoming manifest after an epileptogenic insult to the brain.