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Gene-Environment Interaction in a Conditional NMDAR-Knockout Model of Schizophrenia
Alexei M Bygrave1, Simonas Masiulis1, Dimitri M Kullmann2
1Department of Experimental Psychology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
Frontiers in Behavioral Neuroscience
|January 29, 2019
Summary
Genetic predisposition and environmental stress interact to influence schizophrenia pathology. Reduced environmental enrichment in adulthood exacerbates cognitive deficits in mice with NMDA-receptor hypofunction, highlighting gene-environment interactions in schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Schizophrenia pathogenesis involves complex interactions between genetic susceptibility and environmental risk factors.
- NMDA-receptor (NMDAR) hypofunction in forebrain inhibitory interneurons is implicated in schizophrenia models.
Purpose of the Study:
- To investigate the impact of reduced environmental enrichment in adulthood on schizophrenia-related behavioral domains in a mouse model of NMDAR hypofunction.
- To assess deficits in positive, negative, and cognitive symptoms associated with NMDAR hypofunction under varying environmental conditions.
Main Methods:
- Utilized a mouse line (Grin1ΔPpp1r2) modeling forebrain NMDAR hypofunction in inhibitory interneurons.
- Assessed behavioral phenotypes across positive, negative, and cognitive domains under standard and enriched housing conditions.
- Administered reduced environmental enrichment as an adult stressor.
Main Results:
- Grin1ΔPpp1r2 mice housed in highly enriched environments exhibited largely normal behavior in schizophrenia-related tests.
- Exposure to minimal enrichment in adulthood led to significant short-term memory deficits in these mice.
- These findings suggest a critical interaction between genetic risk and environmental factors.
Conclusions:
- Environmental enrichment can mask cognitive deficits in genetic models of schizophrenia.
- Reduced environmental enrichment acts as a stressor that unmasks cognitive impairments in mice with NMDAR hypofunction.
- Gene-environment interactions are crucial in understanding the development of cognitive dysfunction in schizophrenia.
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