CoChat
Sign Up
Cited by 173Neuroscience and Neuropharmacology ResearchSchizophrenia research and treatmentAmino Acid Enzymes and Metabolism

The DOI matches its Crossref record; 86 of the 87 references it cites were found in a registry or an index.

Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia

Steullet, P., Neijt, H.C., Cuénod, M., Do, K.Q.·2006·Neuroscience
DOI 10.1016/j.neuroscience.2005.10.014
Open this paper in CoChat — free account

Abstract

Increasing evidence suggests that the metabolism of glutathione, an endogenous redox regulator, is abnormal in schizophrenia. Patients show a deficit in glutathione levels in the cerebrospinal fluid and prefrontal cortex and a reduction in gene expression of the glutathione synthesizing enzymes. We investigated whether such glutathione deficit altered synaptic transmission and plasticity in slices of rat hippocampus, with particular emphasis on NMDA receptor function. An approximately 40% decrease in brain glutathione levels was induced by s.c. administration of L-buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis. Such glutathione deficit did not affect the basal synaptic transmission, but produced several NMDA receptor-dependent and -independent effects. Glutathione deficit caused an increase in excitability of CA1 pyramidal cells. The paired-pulse facilitation was diminished in glutathione-depleted slices, in a manner that was independent of NMDA receptor activity. This suggests that lowering glutathione levels altered presynaptic mechanisms involved in neurotransmitter release. NMDA receptor-dependent long-term potentiation induced by high-frequency stimulation was impaired in glutathione-depleted slices. Pharmacologically isolated NMDA receptor-mediated field excitatory postsynaptic potentials were significantly smaller in L-buthionine-(S,R)-sulfoximine-treated than in control slices. Hypofunction of NMDA receptors under glutathione deficit was explained at least in part by an excessive oxidation of the extracellular redox-sensitive sites of the NMDA receptors. These results indicate that a glutathione deficit, like that observed in schizophrenics, alters short- and long-term synaptic plasticity and affects NMDA receptor function. Thus, glutathione deficit could be one causal factor for the hypofunction of NMDA receptors in schizophrenia.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.neuroscience.2005.10.014

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 1

  1. Cabungcal, 2005, Glutathione deficit during development induces anomalies in anterior cingulate GABA interneurones, Schizophr Bull, 31, 258

Cited by

Sorted by citations

See all 173

Related

See all

Metadata

Authors
Steullet, P., Neijt, H. C., Cuénod, M., & Do, K. Q.
Affiliations
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Novartis (Switzerland) (CH)
  • University of Lausanne (CH)
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2006-01
Volume
137
Issue
3
Pages
807-819
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2005.10.014
OpenAlex
W2004830149
Cited by
173
References
87
Citations by year
2025: 4 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 13 · 2020: 6 · 2019: 6 · 2018: 10 · 2017: 12 · 2016: 11 · 2015: 12 · 2014: 11 · 2013: 9 · 2012: 16
FWCI
2.65
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
NMDA receptor hypofunction, synaptic plasticity, schizophrenia, L-buthionine sulfoximine, glutathione synthesis inhibition, paired-pulse facilitation, long-term potentiation, presynaptic neurotransmitter release, hippocampus, glutathione metabolism
MeSH terms
Animals, Antimetabolites, Electric Stimulation, Electrophysiology, Glutamate-Cysteine Ligase, Glutathione, Membrane Potentials, Synaptic Transmission, Neuronal Plasticity, Schizophrenia, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Long-Term Potentiation, Buthionine Sulfoximine, Excitatory Postsynaptic Potentials, Rats, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review