Environmental enrichment slows disease progression in R6/2 Huntington's disease mice.
Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression. Environmental enrichment alters gene expression in the normal mouse brain, and modulates the course of several neurological disorders. Environmentally enriched mice may actually mimic human disease more accurately. We found that even limited environmental enrichment slows decline in RotaRod performance in R6/2 mice, despite rapid disease progression, whereas in normal littermates, maximal enrichment was required to induce a marked improvement in behavioral tests. Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease.
Hockly
Emma
E
Division of Medical and Molecular Genetics, GKT School of Medicine, King's College London, UK. ehockly@hotmail.com
Cordery
Patricia M
PM
Woodman
Benjamin
B
Mahal
Amarbirpal
A
van Dellen
Anton
A
Blakemore
Colin
C
Lewis
Cathryn M
CM
Hannan
Anthony J
AJ
Bates
Gillian P
GP
D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D003594:Cytoplasmic Granules / Q000737:chemistry; D018450:Disease Progression; D004779:Environment Design; D005260:Female; D018737:Hand Strength; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009043:Motor Activity; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D025801:Ubiquitin / Q000032:analysis; D015431:Weight Loss
D010455:Peptides; D025801:Ubiquitin; C097188:polyglutamine