Nektarios K Mazarakis1, Christina Mo2, Thibault Renoir2, Anton van Dellen1, Robert Deacon3, Colin Blakemore1, Anthony J Hannan4. 1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. 2. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia. 3. Department of Experimental Psychology, University of Oxford, Oxford, UK. 4. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia.
Abstract
BACKGROUND: Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment. OBJECTIVE: To assess if a higher level of environmental stimulation ('super-enrichment') has additional benefits compared to home-cage EE in HD mice. METHODS: One group of R6/1 transgenic HD mice and wild-type (WT) littermates were home-cage enriched (EE group). A second group also had enriched home cages, but from 6 weeks of age were exposed to a large 'super-enrichment' arena (SuperE group) three times per week. A range of motor tests (open field, rotarod, clasping) were conducted from 8 weeks of age and, at the end of the experiment, grip strength was assessed and post-mortem measures were taken (brain weight, striatal volume, dopamine receptor activation and aggregate density). RESULTS: SuperE improved the reduction of exploration in the open field, ameliorated impaired grip strength in home-cage enriched HD mice and delayed, but did not abolish, the onset of rear-paw clasping compared to EE. SuperE increased brain weight compared to EE in HD mice and reduced striatal dopamine D1 receptor agonist-induced c-fos expression, regardless of genotype. Body weight, rotarod performance, aggregate formation and striatal volume in SuperE groups were no different compared to EE groups. CONCLUSIONS: The beneficial effects of sensorimotor and cognitive stimulation are graded and extend beyond merely compensating for the deprivation of standard home cages in specific motor-related phenotypes in HD. Our findings highlight the importance of environmental enrichment quality and quantity and the translational value of stimulating living conditions as experience-dependent modulators of pathogenesis in HD and other brain disorders.
BACKGROUND:Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HDmice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment. OBJECTIVE: To assess if a higher level of environmental stimulation ('super-enrichment') has additional benefits compared to home-cage EE in HDmice. METHODS: One group of R6/1 transgenic HDmice and wild-type (WT) littermates were home-cage enriched (EE group). A second group also had enriched home cages, but from 6 weeks of age were exposed to a large 'super-enrichment' arena (SuperE group) three times per week. A range of motor tests (open field, rotarod, clasping) were conducted from 8 weeks of age and, at the end of the experiment, grip strength was assessed and post-mortem measures were taken (brain weight, striatal volume, dopamine receptor activation and aggregate density). RESULTS: SuperE improved the reduction of exploration in the open field, ameliorated impaired grip strength in home-cage enriched HDmice and delayed, but did not abolish, the onset of rear-paw clasping compared to EE. SuperE increased brain weight compared to EE in HDmice and reduced striatal dopamine D1 receptor agonist-induced c-fos expression, regardless of genotype. Body weight, rotarod performance, aggregate formation and striatal volume in SuperE groups were no different compared to EE groups. CONCLUSIONS: The beneficial effects of sensorimotor and cognitive stimulation are graded and extend beyond merely compensating for the deprivation of standard home cages in specific motor-related phenotypes in HD. Our findings highlight the importance of environmental enrichment quality and quantity and the translational value of stimulating living conditions as experience-dependent modulators of pathogenesis in HD and other brain disorders.
Authors: Carlos Henrique Rocha Catalão; Glaucia Yuri Shimizu; Jacqueline Atsuko Tida; Camila Araújo Bernardino Garcia; Antonio Carlos Dos Santos; Carlos Ernesto Garrido Salmon; Maria José Alves Rocha; Luiza da Silva Lopes Journal: Childs Nerv Syst Date: 2017-04-05 Impact factor: 1.475
Authors: Nathalie Percie du Sert; Alessio Alfieri; Stuart M Allan; Hilary Vo Carswell; Graeme A Deuchar; Tracy D Farr; Paul Flecknell; Lindsay Gallagher; Claire L Gibson; Michael J Haley; Malcolm R Macleod; Barry W McColl; Christopher McCabe; Anna Morancho; Lawrence Df Moon; Michael J O'Neill; Isabel Pérez de Puig; Anna Planas; C Ian Ragan; Anna Rosell; Lisa A Roy; Kathryn O Ryder; Alba Simats; Emily S Sena; Brad A Sutherland; Mark D Tricklebank; Rebecca C Trueman; Lucy Whitfield; Raymond Wong; I Mhairi Macrae Journal: J Cereb Blood Flow Metab Date: 2017-08-11 Impact factor: 6.200