A developmental in vivo 1H NMR study in mice with genetic redox dysregulation: an animal model with relevance to schizophrenia

Details

Serval ID
serval:BIB_67FF1F5ECAE4
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
A developmental in vivo 1H NMR study in mice with genetic redox dysregulation: an animal model with relevance to schizophrenia
Title of the conference
22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neurochemistry, Busan, South Korea, August 23-29, 2009
Author(s)
Frank A., Duarte J.M., Do K.Q., Gruetter R.
ISBN
0022-3042
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
110
Series
Journal of Neurochemistry
Pages
97
Language
english
Abstract
Glutathione (GSH), a major redox regulator and anti-oxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse model with 60% decreased brain GSH levels, we have shown that redox dysregulation results in abnormal brain morphology and function. Current theory holds that schizophrenia is a developmental disease involving progressive anatomical and functional brain pathology. Here, we used GCLM KO mice to investigate the impact of a genetically dysregulated redox system on the neurochemical profile of the developing brain. The anterior and posterior cortical neurochemical profile of male and female GCLM KO, heterozygous and wildtype mice was determined by localised in vivo 1H NMR spectroscopy at 14.1 T (Varian/Magnex spectrometer) on post-natal days 10, 20, 30, 60 and 90. We show, for the first time, (1) that high quality 1H NMR spectra can be acquired from early developing mouse brains and (2) that recurrent anaesthesia by itself when administered at the same developmental days has no adverse effects on brain metabolites nor on adult behaviour. (3) Most importantly, our results reveal genotype and age specific changes for a number of metabolites revealing insight into normal brain development and about the impact of genetic GSH dysregulation.
Open Access
Yes
Create date
19/02/2010 12:06
Last modification date
20/08/2019 15:23
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