Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: relevance to schizophrenia

Détails

ID Serval
serval:BIB_C85B77CA4903
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: relevance to schizophrenia
Auteur(s)
Cabungcal Jan Harry, Nicolas D., Kraftsik Rudolf, Cuénod Michel, Do Kim Quang, Hornung J.P.
ISBN
0302-282X
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
54
Série
Neuropsychobiology
Pages
6
Langue
anglais
Notes
SAPHIRID:61719
Résumé
In schizophrenia patients, a decrease in glutathione levels ([GSH]) in cerebrospinal fluid and prefrontal cortex was observed, as well as a decrease in the expression of a gene coding for glutamyl-cysteine ligase (GCL), the limiting enzyme of GSH synthesis. As a redox regulator, GSH plays an important role in protecting cells against oxidative stress. In rat models with a GSH deficit, anomalies analogous to those of patients were observed, such as a decrease in spine number in prefrontal cortex and an alteration of NMDA responses. We aim to find substances that could increase [GSH] in cortical cells and to study the underlying mechanisms. GSH-ethyl-ester (GSHEE) succeeded in replenishing [GSH] in cultured neurons and astrocytes depleted in GSH by BSO, an inhibitor of GCL. GSHEE also abolished dopamine-induced decrease of NMDA-mediated calcium response observed in BSO-treated neurons. Gamma-glutamylcysteine- ethyl-ester (GCEE) increased [GSH] mostly in astrocytes. These results show that GSHEE and GCEE re-establish physiological [GSH] in brain cells by bypassing the limiting step of GSH synthesis. Curcumin (polyphenol), tert-butylhydroquinone (tBHQ; quinone), quercetin (flavonoid) and FK506 (immunosuppressant) were tested for their capacity to boost GSH synthesis. Curcumin was the most efficient. It increased [GSH] by 50 and 100% in non BSO-treated neurons and astrocytes, respectively, and increased GCL activity by more than 100% in astrocytes. In neurons, low concentrations of tBHQ (10-20_M) increased [GSH] by 20% while high [tBHQ] and quercetin led to cell death. In astrocytes, both substances increased [GSH] and GCL activity at rather high concentrations (100_M). FK506 was inefficient in both cell types. These results indicate that neurons and astrocytes are not responding similarly to some of the tested substances, suggesting that the mechanisms regulating GSH synthesis and the susceptibility to oxidative stress might differ in the two cell types.
Open Access
Oui
Création de la notice
10/03/2008 11:49
Dernière modification de la notice
09/05/2019 1:09
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