Cited by 109Epilepsy research and treatmentAmino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology Research

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Regulation of astrocyte glutamine synthetase in epilepsy

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Eid, Tore, Tu, Nathan, Lee, Tih-Shih W., Lai, James C.K.·2013·Neurochemistry International

DOI 10.1016/j.neuint.2013.06.008PMC PMC3825815

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Abstract

Astrocytes play a crucial role in regulating and maintaining the extracellular chemical milieu of the central nervous system under physiological conditions. Moreover, proliferation of phenotypically altered astrocytes (a.k.a. reactive astrogliosis) has been associated with many neurologic and psychiatric disorders, including mesial temporal lobe epilepsy (MTLE). Glutamine synthetase (GS), which is found in astrocytes, is the only enzyme known to date that is capable of converting glutamate and ammonia to glutamine in the mammalian brain. This reaction is important, because a continuous supply of glutamine is necessary for the synthesis of glutamate and GABA in neurons. The known stoichiometry of glutamate transport across the astrocyte plasma membrane also suggests that rapid metabolism of intracellular glutamate via GS is a prerequisite for efficient glutamate clearance from the extracellular space. Several studies have indicated that the activity of GS in astrocytes is diminished in several brain disorders, including MTLE. It has been hypothesized that the loss of GS activity in MTLE leads to increased extracellular glutamate concentrations and epileptic seizures. Understanding the mechanisms by which GS is regulated may lead to novel therapeutic approaches to MTLE, which is frequently refractory to antiepileptic drugs. This review discusses several known mechanisms by which GS expression and function are influenced, from transcriptional control to enzyme modification.

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Authors: Eid, T., Tu, N., Lee, T.-S. W., & Lai, J. C. K.
Affiliations: Yale University (US)
Idaho State University (US)
Corresponding author: Eid, Tore
ORCID: Eid, Tore
Tu, Nathan
Lee, Tih-Shih W.
Venue: Neurochemistry International
Publisher: Elsevier BV
Published: 2013-12
Volume: 63
Issue: 7
Pages: 670-681
ISSN: 0197-0186 (ISSN-L)
DOI: 10.1016/j.neuint.2013.06.008
PMC: PMC3825815
OpenAlex: W2002196897
Cited by: 109
References: 187
Citations by year: 2025: 14 · 2024: 2 · 2023: 5 · 2022: 11 · 2021: 14 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 15 · 2015: 7 · 2014: 7 · 2013: 3
FWCI: 1.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Neurochemistry International (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Neurological Disorders and Stroke (K08NS058674, R01NS070824)
National Center for Research Resources (TL1RR024137, UL1RR024139)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: glutamine synthetase, astrocytes, mesial temporal lobe epilepsy, reactive astrogliosis, glutamate metabolism, glutamate clearance, extracellular glutamate, transcriptional regulation, enzyme modification, drug-resistant epilepsy, GABA synthesis
MeSH terms: Astrocytes, Epilepsy, Temporal Lobe, Glutamate-Ammonia Ligase, Humans

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Regulation of astrocyte glutamine synthetase in epilepsy

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