The DOI matches its Crossref record; 185 of the 187 references it cites were found in a registry or an index.
Regulation of astrocyte glutamine synthetase in epilepsy
Open accessAbstract
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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“This could lead to synaptic loss due to excitotoxicity (6, 33, 34) and reduced synaptogenesis due to the destabilization of nascent synapses (16, 17), which would result in a net loss of synapses during disease progression.”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [33]
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Astrocytes in the initiation and progression of epilepsy
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Metadata
- 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
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 63
- Issue
- 7
- Pages
- 670-681
- ISSN
- 0197-0186 (ISSN-L)
- 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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