N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development.

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State: Public
Version: author
Serval ID
serval:BIB_E4BB7B8743F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development.
Journal
Biological Psychiatry
Author(s)
das Neves Duarte J.M., Kulak A., Gholam-Razaee M.M., Cuenod M., Gruetter R., Do K.Q.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
71
Number
11
Pages
1006-1014
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
BACKGROUND: Glutathione (GSH) is the major cellular redox-regulator and antioxidant. Redox-imbalance due to genetically impaired GSH synthesis is among the risk factors for schizophrenia. Here we used a mouse model with chronic GSH deficit induced by knockout (KO) of the key GSH-synthesizing enzyme, glutamate-cysteine ligase modulatory subunit (GCLM).¦METHODS: With high-resolution magnetic resonance spectroscopy at 14.1 T, we determined the neurochemical profile of GCLM-KO, heterozygous, and wild-type mice in anterior cortex throughout development in a longitudinal study design.¦RESULTS: Chronic GSH deficit was accompanied by an elevation of glutamine (Gln), glutamate (Glu), Gln/Glu, N-acetylaspartate, myo-Inositol, lactate, and alanine. Changes were predominantly present at prepubertal ages (postnatal days 20 and 30). Treatment with N-acetylcysteine from gestation on normalized most neurochemical alterations to wild-type level.¦CONCLUSIONS: Changes observed in GCLM-KO anterior cortex, notably the increase in Gln, Glu, and Gln/Glu, were similar to those reported in early schizophrenia, emphasizing the link between redox imbalance and the disease and validating the model. The data also highlight the prepubertal period as a sensitive time for redox-related neurochemical changes and demonstrate beneficial effects of early N-acetylcysteine treatment. Moreover, the data demonstrate the translational value of magnetic resonance spectroscopy to study brain disease in preclinical models.
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Create date
21/05/2012 15:45
Last modification date
20/08/2019 17:08
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