Titre
Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Monin, A.
Auteure/Auteur
Baumann, P.S.
Auteure/Auteur
Griffa, A.
Auteure/Auteur
Xin, L.
Auteure/Auteur
Mekle, R.
Auteure/Auteur
Fournier, M.
Auteure/Auteur
Butticaz, C.
Auteure/Auteur
Klaey, M.
Auteure/Auteur
Cabungcal, J.H.
Auteure/Auteur
Steullet, P.
Auteure/Auteur
Ferrari, C.
Auteure/Auteur
Cuenod, M.
Auteure/Auteur
Gruetter, R.
Auteure/Auteur
Thiran, J.P.
Auteure/Auteur
Hagmann, P.
Auteure/Auteur
Conus, P.
Auteure/Auteur
Do, K.Q.
Auteure/Auteur
Liens vers les unités
ISSN
1476-5578
Statut éditorial
Publié
Date de publication
2015-07
Volume
20
Numéro
7
Première page
827
Dernière page/numéro d’article
838
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia.
Sujets
PID Serval
serval:BIB_E4804562B409
PMID
Date de création
2014-11-07T09:40:18.221Z
Date de création dans IRIS
2025-05-21T06:41:29Z
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Nom
25155877.pdf
Version du manuscrit
postprint
Taille
1.85 MB
Format
Adobe PDF
PID Serval
serval:BIB_E4804562B409.P002
URN
urn:nbn:ch:serval-BIB_E4804562B4094
Somme de contrôle
(MD5):40920d3ddc4b5fa2f08424c40dc9eb46