ArticleProceedings of the National Academy of Sciences of the United States of America2019
The glutathione cycle shapes synaptic glutamate activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
80 citing papers in PubMed, 152 citations in OpenAlex.
- The effect of acupuncture on depression and its correlation with metabolic alterations: A randomized controlled trial.Medicine · 2020Trial
- Effects of acute N-acetylcysteine challenge on cortical glutathione and glutamate in schizophrenia: A pilot in vivo proton magnetic resonance spectroscopy study.Psychiatry research · 2019Trial
- Double DANTE-PRESS: Development of a 1H-MRS Multifrequency-Selective Sequence for Simultaneous In Vivo Quantification of Glutathione and Glutamate at 7 Tesla.NMR in biomedicine · 2026Article
- The Glutamate-Glutathione axis in neuropsychiatric disorders and cancer: From shared mechanisms to non-invasive biomarkers.Redox biology · 2026Review
- Using combined ROC curves to improve the diagnostic usefulness of glutaminase, prostaglandins, and 8-isoprostane as biomarkers of autism spectrum disorders;Role in the Glu-GABA-Gln cycle.BMC neuroscience · 2026Article
- Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes.International journal of molecular sciences · 2026Review
- The interactions of copper, glutamate, and cuproptosis: insights into brain health and Alzheimer's disease pathology.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability.Journal of neurochemistry · 2026Review
- Hungry for Knowledge: Octopamine Signaling Regulates Hunger-Enhanced Olfactory Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis in Cerebral Ischemia/Reperfusion Injury: Mechanistic Drivers and Therapeutic Frontiers.Neuropsychiatric disease and treatment · 2026Review
- From gut to brain: short-term ketogenic diet alleviates status epilepticus-induced cognitive deficits in rats.Frontiers in physiology · 2026Article
- The Impaired Response Inhibition and Salience Attribution Model of Drug Addiction: Recent Neuroimaging Evidence and Future Directions.Annual review of psychology · 2026Review
- Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids.Cellular and molecular life sciences : CMLS · 2025Article
- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
- Exploring salivary metabolites as biomarkers in chronic craniofacial and orofacial pain: a metabolomic analysis.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Association of GRM7 Polymorphisms with Bilateral Auditory Regions Glutamate and Coupling with Glutathione in ARHL Patients.Molecular neurobiology · 2025Article
- Herbal Weight Loss Supplements Induce Metabolomic In Vitro Changes Indicative of Oxidative Stress.Metabolites · 2025Article
- dVGLUT Is a Mediator of Sex Differences in Dopamine Neuron Mitochondrial Function Across Aging and in a Parkinson's Disease Model.Aging cell · 2025Article
- Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Glutathione Metabolism of the Brain-The Role of Astrocytes.Journal of neurochemistry · 2025Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Glutamate is the most abundant excitatory neurotransmitter, present at the bulk of cortical synapses, and participating in many physiologic and pathologic processes ranging from learning and memory to stroke. The tripeptide, glutathione, is one-third glutamate and present at up to low millimolar intracellular concentrations in brain, mediating antioxidant defenses and drug detoxification. Because of the substantial amounts of brain glutathione and its rapid turnover under homeostatic control, we hypothesized that glutathione is a relevant reservoir of glutamate and could influence synaptic excitability. We find that drugs that inhibit generation of glutamate by the glutathione cycle elicit decreases in cytosolic glutamate and decreased miniature excitatory postsynaptic potential (mEPSC) frequency. In contrast, pharmacologically decreasing the biosynthesis of glutathione leads to increases in cytosolic glutamate and enhanced mEPSC frequency. The glutathione cycle can compensate for decreased excitatory neurotransmission when the glutamate-glutamine shuttle is inhibited. Glutathione may be a physiologic reservoir of glutamate neurotransmitter.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.