responses to environmental enrichment differ with sex and genotype in a transgenic mouse model of huntingtons disease应对环境浓缩与性和不同基因型在亨廷顿氏舞蹈症的转基因小鼠模型.pdfVIP

Responses to Environmental Enrichment Differ with Sex and Genotype in a Transgenic Mouse Model of Huntington’s Disease Nigel I. Wood*, Valentina Carta, Stefan Milde, Elizabeth A. Skillings, Catherine J. McAllister, Y.L. Mabel Ang, Alasdair Duguid, Nadeev Wijesuriya, Samira Mohd Afzal, Joe X. Fernandes, T.W. Leong, Jennifer Morton Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom 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. Methodology/Principal Findings: 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