{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T22:53:07Z","timestamp":1771023187813,"version":"3.50.1"},"reference-count":76,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T00:00:00Z","timestamp":1501200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["148250"],"award-info":[{"award-number":["148250"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31\u2010116689"],"award-info":[{"award-number":["31\u2010116689"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats: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 (\u2212\/\u2212) of the glutamate\u2010cysteine ligase modulatory subunit (<jats:italic>Gclm<\/jats:italic>) was exposed to social isolation stress from weaning to post\u2010natal day 65. Using magnetic resonance methods at high\u2010field (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 <jats:italic>N<\/jats:italic>\u2010acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine\u2010to\u2010glutamate (Gln\/Glu), and by a reduction in levels of <jats:italic>myo\u2010<\/jats:italic>inositol and choline\u2010containing compounds in the frontal cortex of \u2212\/\u2212 animals with respect to wild\u2010type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower <jats:italic>myo\u2010<\/jats:italic>inositol concentration (\u22128.4%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) and larger Gln\/Glu (+7.6%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), 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.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14116-fig-0003-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14116","type":"journal-article","created":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T06:12:40Z","timestamp":1498803160000},"page":"767-775","source":"Crossref","is-referenced-by-count":16,"title":["Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine\u2010to\u2010glutamate ratio and <i>myo<\/i>\u2010inositol concentration in the mouse frontal cortex"],"prefix":"10.1111","volume":"142","author":[{"given":"Alberto","family":"Corcoba","sequence":"first","affiliation":[{"name":"Laboratory for Functional and Metabolic Imaging \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"},{"name":"Department of Psychiatry Center for Psychiatric Neuroscience Lausanne University Hospital Prilly\u2010Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Gruetter","sequence":"additional","affiliation":[{"name":"Laboratory for Functional and Metabolic Imaging \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"},{"name":"Department of Radiology University of Lausanne Lausanne Switzerland"},{"name":"Department of Radiology University of Geneva Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim Q.","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Psychiatric Neuroscience Lausanne University Hospital Prilly\u2010Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-1574","authenticated-orcid":false,"given":"Jo\u00e3o M.N.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Laboratory for Functional and Metabolic Imaging \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-16-06241.1998"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.02.017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhi048"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.10.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.121"},{"key":"e_1_2_8_7_1","first-page":"611","article-title":"Glutamatergic and neuronal dysfunction in gray and white matter: a spectroscopic Imaging study in a large schizophrenia sample","volume":"43","author":"Bustillo J. 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