N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during developmentReport as inadecuate




N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development - Download this document for free, or read online. Document in PDF available to download.

Published in: Biological Psychiatry, vol. 71, num. 11, p. 1006-1014 Publication date: 2012

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. © 2012 Society of Biological Psychiatry.

Keywords: CIBM-AIT Reference EPFL-ARTICLE-177420doi:10.1016/j.biopsych.2011.07.035





Author: Das Neves Duarte, J. M.; Kulak, A.; Gholam-Razaee, M. M.; Cuenod, M.; Gruetter, R.; Do, K. Q.

Source: https://infoscience.epfl.ch/record/177420?ln=en







Related documents