Environmental Enrichment and Gene–Environment Interactions in Mouse Models of Brain Disorders

Author(s):  
Anthony J. Hannan
2016 ◽  
Vol 100 ◽  
pp. 2-16 ◽  
Author(s):  
Kevin K. Ogden ◽  
Emin D. Ozkan ◽  
Gavin Rumbaugh
Keyword(s):  

2004 ◽  
Vol 51 (2) ◽  
pp. 415-430 ◽  
Author(s):  
Anthony J Hannan

Huntington's disease (HD) is an autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This review outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of 'enviromimetics' which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.


2017 ◽  
Vol 81 (10) ◽  
pp. S299
Author(s):  
Flurin Cathomas ◽  
Damiano Azzinnari ◽  
Giorgio Bergamini ◽  
Hannes Sigrist ◽  
Michaela Buerge ◽  
...  

2018 ◽  
Vol 373 (1756) ◽  
pp. 20170289 ◽  
Author(s):  
Bruno Sauce ◽  
Sophie Bendrath ◽  
Margalit Herzfeld ◽  
Dan Siegel ◽  
Conner Style ◽  
...  

General cognitive ability can be highly heritable in some species, but at the same time, is very malleable. This apparent paradox could potentially be explained by gene–environment interactions and correlations that remain hidden due to experimental limitations on human research and blind spots in animal research. Here, we shed light on this issue by combining the design of a sibling study with an environmental intervention administered to laboratory mice. The analysis included 58 litters of four full-sibling genetically heterogeneous CD-1 male mice, for a total of 232 mice. We separated the mice into two subsets of siblings: a control group (maintained in standard laboratory conditions) and an environmental-enrichment group (which had access to continuous physical exercise and daily exposure to novel environments). We found that general cognitive ability in mice has substantial heritability (24% for all mice) and is also malleable. The mice that experienced the enriched environment had a mean intelligence score that was 0.44 standard deviations higher than their siblings in the control group (equivalent to gains of 6.6 IQ points in humans). We also found that the estimate of heritability changed between groups (55% in the control group compared with non-significant 15% in the enrichment group), analogous to findings in humans across socio-economic status. Unexpectedly, no evidence of gene–environment interaction was detected, and so the change in heritability might be best explained by higher environmental variance in the enrichment group. Our findings, as well as the ‘sibling intervention procedure’ for mice, may be valuable to future research on the heritability, mechanisms and evolution of cognition. This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.


2013 ◽  
Vol 3 (9) ◽  
pp. e304-e304 ◽  
Author(s):  
B Barak ◽  
I Shvarts-Serebro ◽  
S Modai ◽  
A Gilam ◽  
E Okun ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-25 ◽  
Author(s):  
Mustafa Varçin ◽  
Eduard Bentea ◽  
Yvette Michotte ◽  
Sophie Sarre

There is extensive evidence in Parkinson’s disease of a link between oxidative stress and some of the monogenically inherited Parkinson’s disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson’s disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson’s disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson’s disease, gene-environment interactions in genetically engineered mouse models of Parkinson’s disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson’s disease.


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