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Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex

Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q and Duarte, João M N LU (2017) In Journal of Neurochemistry 142(5). p.767-775
Abstract

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations... (More)

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p < 0.05) and larger Gln/Glu (+7.6%, p < 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Frontal Lobe, Glutamic Acid, Glutamine, Glutathione, Inositol, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Social Isolation, Stress, Psychological, Journal Article
in
Journal of Neurochemistry
volume
142
issue
5
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85026427137
ISSN
1471-4159
DOI
10.1111/jnc.14116
language
English
LU publication?
no
id
c233df39-f697-4b77-b377-6f29550af744
date added to LUP
2017-10-19 15:03:31
date last changed
2018-01-07 12:22:55
@article{c233df39-f697-4b77-b377-6f29550af744,
  abstract     = {<p>Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p &lt; 0.05) and larger Gln/Glu (+7.6%, p &lt; 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis.</p>},
  author       = {Corcoba, Alberto and Gruetter, Rolf and Do, Kim Q and Duarte, João M N},
  issn         = {1471-4159},
  keyword      = {Animals,Frontal Lobe,Glutamic Acid,Glutamine,Glutathione,Inositol,Male,Mice,Mice, Inbred C57BL,Mice, Knockout,Social Isolation,Stress, Psychological,Journal Article},
  language     = {eng},
  number       = {5},
  pages        = {767--775},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex},
  url          = {http://dx.doi.org/10.1111/jnc.14116},
  volume       = {142},
  year         = {2017},
}