Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_C3341BECC5AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.
Périodique
Schizophrenia bulletin
Auteur(s)
Xin L., Mekle R., Fournier M., Baumann P.S., Ferrari C., Alameda L., Jenni R., Lu H., Schaller B., Cuenod M., Conus P., Gruetter R., Do K.Q.
ISSN
1745-1701 (Electronic)
ISSN-L
0586-7614
Statut éditorial
Publié
Date de publication
09/2016
Peer-reviewed
Oui
Volume
42
Numéro
5
Pages
1185-1196
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Oxidative stress and glutathione (GSH) metabolism dysregulation has been implicated in the pathophysiology of schizophrenia. GAG-trinucleotide repeat (TNR) polymorphisms in the glutamate-cysteine ligase catalytic gene (GCLC), the rate-limiting enzyme for GSH synthesis, are associated with schizophrenia. In addition, GSH may serve as a reserve pool for neuronal glutamate (Glu) through the γ-glutamyl cycle. The aim of this study is to investigate brain [GSH] and its association with GCLC polymorphism, peripheral redox indices and brain Glu.
Magnetic resonance spectroscopy was used to measure [GSH] and [Glu] in the medial prefrontal cortex (mPFC) of 25 early-psychosis patients and 33 controls. GCLC polymorphism was genotyped, glutathione peroxidases (GPx) and glutathione reductase (GR) activities were determined in blood cells.
Significantly lower [GSHmPFC] in GCLC high-risk genotype subjects were revealed as compared to low-risk genotype subjects independent of disease status. In male subjects, [GSHmPFC] and blood GPx activities correlate positively in controls (P = .021), but negatively in patients (P = .039). In GCLC low-risk genotypes, [GlumPFC] are lower in patients, while it is not the case for high-risk genotypes.
GCLC high-risk genotypes are associated with low [GSHmPFC], highlighting that GCLC polymorphisms should be considered in pathology studies of cerebral GSH. Low brain GSH levels are related to low peripheral oxidation status in controls but with high oxidation status in patients, pointing to a dysregulated GSH homeostasis in early psychosis patients. GCLC polymorphisms and disease associated correlations between brain GSH and Glu levels may allow patients stratification.

Mots-clé
Adult, Female, Genotype, Glutamate-Cysteine Ligase/genetics, Glutamic Acid/metabolism, Glutathione/metabolism, Glutathione Peroxidase/metabolism, Humans, Magnetic Resonance Spectroscopy, Male, Oxidation-Reduction, Oxidative Coupling, Polymorphism, Genetic, Prefrontal Cortex/diagnostic imaging, Prefrontal Cortex/metabolism, Psychotic Disorders/diagnostic imaging, Psychotic Disorders/metabolism, Young Adult, GCLC, MRS, glutamate, glutathione, glutathione peroxidase, oxidative stress, redox, schizophrenia
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/04/2016 13:37
Dernière modification de la notice
20/08/2019 16:38
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