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Gene-Environment Interaction in a Conditional NMDAR-Knockout Model of Schizophrenia

Bygrave, AM; Masiulis, S; Kullmann, DM; Bannerman, DM; Kaetzel, D; (2019) Gene-Environment Interaction in a Conditional NMDAR-Knockout Model of Schizophrenia. Frontiers in Behavioral Neuroscience , 12 , Article 332. 10.3389/fnbeh.2018.00332. Green open access

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Abstract

Interactions between genetic and environmental risk factors take center stage in the pathology of schizophrenia. We assessed if the stressor of reduced environmental enrichment applied in adulthood provokes deficits in the positive, negative or cognitive symptom domains of schizophrenia in a mouse line modeling NMDA-receptor (NMDAR) hypofunction in forebrain inhibitory interneurons (Grin1∆Ppp1r2 ). We find that Grin1∆Ppp1r2 mice, when group-housed in highly enriched cages, appear largely normal across a wide range of schizophrenia-related behavioral tests. However, they display various short-term memory deficits when exposed to minimal enrichment. This demonstrates that the interaction between risk genes causing NMDA-receptor hypofunction and environmental risk factors may negatively impact cognition later in life.

Type: Article
Title: Gene-Environment Interaction in a Conditional NMDAR-Knockout Model of Schizophrenia
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fnbeh.2018.00332
Publisher version: https://doi.org/10.3389/fnbeh.2018.00332
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Behavioral Sciences, Neurosciences, Neurosciences & Neurology, schizophrenia, gene-environment interaction, NMDAR-receptor hypofunction, interneurons, risk factors, EXPRESSED EMOTION, OXIDATIVE STRESS, INTERNEURONS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10068479
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