Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease
Neurobiology of Sleep and Circadian Rhythms
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Ouk, K., Aungier, J., & Morton, J. (2017). Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease. Neurobiology of Sleep and Circadian Rhythms, 2 27-38. https://doi.org/10.1016/j.nbscr.2016.11.004
The circadian disruption seen in patients of Huntington's disease (HD) is recapitulated in the R6/2 mouse model. As the disease progresses, the activity of R6/2 mice increases dramatically during the rest (light) period and decreases during the active (dark) period, eventually leading to a complete disintegration of rest-activity rhythms by the age of ~16 weeks. The suprachiasmatic nucleus controls circadian rhythms by entraining the rest-activity rhythms to the environmental light-dark cycle. Since R6/2 mice can shift their rest-activity rhythms in response to a jet-lag paradigm and also respond positively to bright light therapy (1000 lx), we investigated whether or not a prolonged day length exposure could reduce their daytime activity and improve their behavioural circadian rhythms. We found that a long-day photoperiod (16 h light/8 h dark cycle; 100 lx) significantly improved the survival of R6/2 female mice by 2.4 weeks, compared to mice kept under standard conditions (12 h light/12 h dark cycle). Furthermore, a long-day photoperiod improved the nocturnality of R6/2 female mice. Mice kept under long-day photoperiod also maintained acrophase in activity rhythms (a parameter of rhythmicity strength) in phase with that of WT mice, even if they were symptomatic. By contrast, a short-day photoperiod (8 h light/16 h dark cycle) was deleterious to R6/2 female mice and further reduced the survival by ~1 week. Together, our results support the idea that light therapy may be beneficial for improving circadian dysfunction in HD patients.
This research was supported by a grant from CHDIInc.
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External DOI: https://doi.org/10.1016/j.nbscr.2016.11.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262503
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