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Research ArticleNew Research, Disorders of the Nervous System

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington’s Disease

Huei-Bin Wang, Dawn H. Loh, Daniel S. Whittaker, Tamara Cutler, David Howland and Christopher S. Colwell
eNeuro 2 January 2018, 5 (1) ENEURO.0431-17.2017; https://doi.org/10.1523/ENEURO.0431-17.2017
Huei-Bin Wang
1Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, Los Angeles, CA 90024-1759
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Dawn H. Loh
1Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, Los Angeles, CA 90024-1759
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Daniel S. Whittaker
1Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, Los Angeles, CA 90024-1759
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Tamara Cutler
1Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, Los Angeles, CA 90024-1759
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David Howland
2CHDI Foundation, Princeton, NJ 08540
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Christopher S. Colwell
1Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, Los Angeles, CA 90024-1759
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Abstract

Huntington’s disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays.

  • time-restricted feeding
  • fast/feed cycle
  • circadian rhythms
  • Huntington’s disease
  • Q175

Footnotes

  • The authors declare no competing financial interests.

  • This work was support by the CHDI Foundation Grant A-7293.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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January/February 2018
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Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington’s Disease
Huei-Bin Wang, Dawn H. Loh, Daniel S. Whittaker, Tamara Cutler, David Howland, Christopher S. Colwell
eNeuro 2 January 2018, 5 (1) ENEURO.0431-17.2017; DOI: 10.1523/ENEURO.0431-17.2017

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Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington’s Disease
Huei-Bin Wang, Dawn H. Loh, Daniel S. Whittaker, Tamara Cutler, David Howland, Christopher S. Colwell
eNeuro 2 January 2018, 5 (1) ENEURO.0431-17.2017; DOI: 10.1523/ENEURO.0431-17.2017
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Keywords

  • time-restricted feeding
  • fast/feed cycle
  • circadian rhythms
  • Huntington’s disease
  • Q175

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