Circadian Dysfunction in Huntington’s Disease

2014 ◽  
pp. 321-338
Author(s):  
Dika Kuljis ◽  
Analyne M. Schroeder ◽  
Takashi Kudo ◽  
Dawn H. Loh ◽  
Christopher S. Colwell
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Circadian Dysfunction

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

eNeuro ◽  
2018 ◽  
Vol 5 (1) ◽  
pp. ENEURO.0431-17.2017 ◽  
Author(s):  
Huei-Bin Wang ◽  
Dawn H. Loh ◽  
Daniel S. Whittaker ◽  
Tamara Cutler ◽  
David Howland ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Motor Symptoms ◽  
Restricted Feeding ◽  
Circadian Dysfunction

scholarly journals Circadian-based Treatment Strategy Effective in the BACHD Mouse Model of Huntington’s Disease

2018 ◽  
Vol 33 (5) ◽  
pp. 535-554 ◽  
Author(s):  
Daniel S. Whittaker ◽  
Dawn H. Loh ◽  
Huei-Bin Wang ◽  
Yu Tahara ◽  
Dika Kuljis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Sleep Onset ◽  
Lifestyle Changes ◽  
Disease Stage ◽  
Preclinical Model ◽  
Delay Disease Progression ◽  
Circadian Dysfunction

Huntington’s disease (HD) patients suffer from 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 excessive fatigue. The BACHD mouse model exhibits many HD core symptoms including circadian dysfunction. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. We evaluated the effects of time-restricted feeding (TRF) on the BACHD mouse model. At 3 months of age, the animals were divided into 2 groups: ad lib and TRF. The TRF-treated BACHD mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle (ZT 15-21) of the period when mice are normally active (ZT 12-24). Following 3 months of treatment (when mice reached the early disease stage), the TRF-treated BACHD mice showed improvements in their locomotor activity and sleep behavioral rhythms. Furthermore, we found improved heart rate variability, suggesting that their autonomic nervous system dysfunction was improved. On a molecular level, TRF altered the phase but not the amplitude of the PER2::LUC rhythms measured in vivo and in vitro. Importantly, treated BACHD mice exhibited improved motor performance compared with untreated BACHD controls, and the motor improvements were correlated with improved circadian output. It is worth emphasizing that HD is a genetically caused disease with no known cure. Lifestyle changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of circadian-based treatment strategies in a preclinical model of HD.

scholarly journals Circadian dysfunction in the Q175 model of Huntington's disease: Network analysis

2019 ◽  
Author(s):  
Benjamin Smarr ◽  
Tamara Cutler ◽  
Dawn H. Loh ◽  
Takashi Kudo ◽  
Dika Kuljis ◽  
...  
Keyword(s):  
Network Analysis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Network ◽  
Circadian Dysfunction

scholarly journals Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington’s Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0147583 ◽  
Author(s):  
Dika A. Kuljis ◽  
Laura Gad ◽  
Dawn H. Loh ◽  
Zoë MacDowell Kaswan ◽  
Olivia N. Hitchcock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Circadian Dysfunction

scholarly journals Blue light therapy improves circadian dysfunction as well as motor symptoms in two mouse models of Huntington's disease

2017 ◽  
Vol 2 ◽  
pp. 39-52 ◽  
Author(s):  
Huei-Bin Wang ◽  
Daniel S. Whittaker ◽  
Danny Truong ◽  
Aly K. Mulji ◽  
Cristina A. Ghiani ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Blue Light ◽  
Light Therapy ◽  
Motor Symptoms ◽  
Circadian Dysfunction

scholarly journals HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease

2021 ◽  
Author(s):  
Pavitra Prakash ◽  
Arpit Kumar Pradhan ◽  
Vasu Sheeba
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Chaperones ◽  
Therapeutic Implications ◽  
Pigment Dispersing Factor ◽  
Drosophila Model ◽  
First Time ◽  
Circadian Dysfunction

Circadian disturbances are early features of neurodegenerative diseases, including Huntington's Disease (HD), affecting the quality of life of patients and caregivers. Emerging evidence suggests that circadian decline feeds-forward to neurodegenerative symptoms, exacerbating them, highlighting a need for restoring circadian health. Therefore, we asked whether any of the known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. Notably, the molecular chaperones HSP40 and HSP70 (Heat Shock Protein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator of HD-induced deficits. Upon HSP40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rhythm rescue was associated with neuronal rescue of loss in circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence for the first time that implicates the neuroprotective chaperone HSP40 in circadian rehabilitation. Given the importance of proteostasis and circadian health in neurodegenerative diseases, the involvement of molecular chaperones in circadian maintenance has broader therapeutic implications.

Sign in / Sign up

Export Citation Format

Share Document