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Joao Duarte

Research team manager

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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

Author

  • Alberto Corcoba
  • Rolf Gruetter
  • Kim Q Do
  • João M N Duarte

Summary, in English

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.

Publishing year

2017-09

Language

English

Pages

767-775

Publication/Series

Journal of Neurochemistry

Volume

142

Issue

5

Document type

Journal article

Publisher

Wiley-Blackwell

Keywords

  • Animals
  • Frontal Lobe
  • Glutamic Acid
  • Glutamine
  • Glutathione
  • Inositol
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Social Isolation
  • Stress, Psychological
  • Journal Article

Status

Published

ISBN/ISSN/Other

  • ISSN: 1471-4159