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Author (up) Wang, H.-B.; Whittaker, D.S.; Truong, D.; Mulji, A.K.; Ghiani, C.A.; Loh, D.H.; Colwell, C.S. url  doi
  Title Blue light therapy improves circadian dysfunction as well as motor symptoms in two mouse models of Huntington's disease Type Journal Article
  Year 2017 Publication Neurobiology of Sleep and Circadian Rhythms Abbreviated Journal Neurobiology of Sleep and Circadian Rhythms  
  Volume 2 Issue Pages 39-52  
  Keywords animals; Human Health  
  Abstract Patients with Huntington's disease (HD) exhibit movement disorders, psychiatric disturbance and cognitive impairments as the disease progresses. Abnormal sleep/wake cycles are common among HD patients with reports of delayed sleep onset, fatigue during the day, and a delayed pattern of melatonin secretion all of which suggest circadian dysfunction. Mouse models of HD confirm disrupted circadian rhythms with pathophysiology found in the central circadian clock (suprachiasmatic nucleus). Importantly, circadian dysfunction manifests early in disease, even before the classic motor symptoms, in both patients and mouse models. Therefore, we hypothesize that the circadian dysfunction may interact with the disease pathology and exacerbate the HD symptoms. If correct, early intervention may benefit patients and delay disease progression. One test of this hypothesis is to determine whether light therapy designed to strengthen this intrinsic timing system can delay the disease progression in mouse models. Therefore, we determined the impact of blue wavelength-enriched light on two HD models: the BACHD and Q175 mice. Both models received 6 hours of blue-light at the beginning of their daily light cycle for 3 months. After treatment, both genotypes showed improvements in their locomotor activity rhythm without significant change to their sleep behavior. Critically, treated mice of both lines exhibited improved motor performance compared to untreated controls. Focusing on the Q175 genotype, we sought to determine whether the treatment altered signaling pathways in brain regions known to be impacted by HD using NanoString gene expression assays. We found that the expression of several HD relevant markers was altered in the striatum and cortex of the treated mice. Our study demonstrates that strengthening the circadian system can delay the progression of HD in pre-clinical models. This work suggests that lighting conditions should be considered when managing treatment of HD and other neurodegenerative disorders.  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2451-9944 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number LoNNe @ kyba @ Serial 1626  
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