title: Responses to environmental enrichment differ with sex and genotype in a transgenic mouse model of Huntington's disease.
abstract: BACKGROUND
  Environmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival.
  
  
  RESULTS
  We examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an "enriched" environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The "home cage" and "playground" groups were subdivided into "handling" (stimulated throughout the experimental period) and "no-handling" groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice.
  
  
  CONCLUSIONS
  We show that even when mice are living in an enriched home cage, further EE had beneficial effects. However, the improvements in cognition and survival vary with sex and genotype. These results indicate that EE may improve the quality of life of HD patients, but we suggest that EE as a therapy should be tailored to individuals.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom. niw20@cam.ac.uk
authors.forename: Nigel I
authors.initials: NI
authors.lastname: Wood
authors.forename: Valentina
authors.initials: V
authors.lastname: Carta
authors.forename: Stefan
authors.initials: S
authors.lastname: Milde
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Skillings
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: McAllister
authors.forename: Y L Mabel
authors.initials: YL
authors.lastname: Ang
authors.forename: Alasdair
authors.initials: A
authors.lastname: Duguid
authors.forename: Nadeev
authors.initials: N
authors.lastname: Wijesuriya
authors.forename: Samira Mohd
authors.initials: SM
authors.lastname: Afzal
authors.forename: Joe X
authors.initials: JX
authors.lastname: Fernandes
authors.forename: T W
authors.initials: TW
authors.lastname: Leong
authors.forename: A Jennifer
authors.initials: AJ
authors.lastname: Morton
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morton
mesh_terms: D000822:Animal Husbandry / Q000379:methods; D000818:Animals; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004779:Environment Design; D005260:Female; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009043:Motor Activity; D045442:Rotarod Performance Test; D012737:Sex Factors; D016019:Survival Analysis; D013550:Swimming; D019680:Trinucleotide Repeat Expansion / Q000235:genetics