ArticleBiochemical and biophysical research communications2011
Glutathione is a physiologic reservoir of neuronal glutamate.
Article in Biochemical and biophysical research communications, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- 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
- Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes.International journal of molecular sciences · 2026Review
- Association of GRM7 Polymorphisms with Bilateral Auditory Regions Glutamate and Coupling with Glutathione in ARHL Patients.Molecular neurobiology · 2025Article
- Membrane ATPases and Mitochondrial Proteins in Fetal Cerebellum After Exposure to L-Glutamate During Gestation.Membranes · 2025Article
- Article
- Review
- Early metabolic alterations in the normal‑appearing grey and white matter of patients with clinically isolated syndrome suggestive of multiple sclerosis: A proton MR spectroscopic study.Experimental and therapeutic medicine · 2023Article
- Glutathione in the nucleus accumbens regulates motivation to exert reward-incentivized effort.eLife · 2022Article
- Oxidative Stress and Emergence of Psychosis.Antioxidants (Basel, Switzerland) · 2022Review
- N-Acetylcysteine and Aripiprazole Improve Social Behavior and Cognition and Modulate Brain BDNF Levels in a Rat Model of Schizophrenia.International journal of molecular sciences · 2022Article
- Forgetting generates a novel state that is reactivatable.Science advances · 2022Article
- Glutathione in Brain Disorders and Aging.Molecules (Basel, Switzerland) · 2022Review
- Article
- Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?Antioxidants (Basel, Switzerland) · 2021Review
- Testing the combined effects of probiotics and prebiotics against neurotoxic effects of propionic acid orally administered to rat pups.Food science & nutrition · 2021Article
- A multimodal approach to studying the relationship between peripheral glutathione, brain glutamate, and cognition in health and in schizophrenia.Molecular psychiatry · 2021Article
- Effectiveness of N-acetylcysteine in Treating Clinical Symptoms of Substance Abuse and Dependence: A Meta-analysis of Randomized Controlled Trials.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2021Article
- Schizophrenia Increases Variability of the Central Antioxidant System: A Meta-Analysis of Variance From MRS Studies of Glutathione.Frontiers in psychiatry · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Glutamate, the principal excitatory neurotransmitter of the brain, participates in a multitude of physiologic and pathologic processes, including learning and memory. Glutathione, a tripeptide composed of the amino acids glutamate, cysteine, and glycine, serves important cofactor roles in antioxidant defense and drug detoxification, but glutathione deficits occur in multiple neuropsychiatric disorders. Glutathione synthesis and metabolism are governed by a cycle of enzymes, the γ-glutamyl cycle, which can achieve intracellular glutathione concentrations of 1-10mM. Because of the considerable quantity of brain glutathione and its rapid turnover, we hypothesized that glutathione may serve as a reservoir of neural glutamate. We quantified glutamate in HT22 hippocampal neurons, PC12 cells and primary cortical neurons after treatment with molecular inhibitors targeting three different enzymes of the glutathione metabolic cycle. Inhibiting 5-oxoprolinase and γ-glutamyl transferase, enzymes that liberate glutamate from glutathione, leads to decreases in glutamate. In contrast, inhibition of γ-glutamyl cysteine ligase, which uses glutamate to synthesize glutathione, results in substantial glutamate accumulation. Increased glutamate levels following inhibition of glutathione synthesis temporally precede later effects upon oxidative stress.
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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.