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Prolonged day length exposure improves circadian deficits and survival in a transgenic mouse model of Huntington's disease

Published version
Peer-reviewed

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Authors

Ouk, K 
Morton, AJ 

Abstract

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.

Description

Keywords

ANOVA, analysis of variance, DD, constant darkness, Depression, EEG, electroencephalography, Estrogen, HD, Huntington's disease, HPA axis, hypothalamic-pituitary-adrenal axis, L-DOPA, levodopa, LD, light-dark, Lifespan, REM sleep, rapid eye movement sleep, SCN, suprachiasmatic nucleus, Sleep, Transgenic mouse, WT, wild type

Journal Title

Neurobiology of Sleep and Circadian Rhythms

Conference Name

Journal ISSN

2451-9944
2451-9944

Volume Title

2

Publisher

Elsevier
Sponsorship
This research was supported by a grant from CHDIInc.