Sleep and Circadian Dysfunction in Neurodegenerative Disorders: Insights from a Mouse Model of Huntington's Disease

Overview

Journal Minerva Pneumol

Specialty Pulmonary Medicine

Date 2013 May 21

PMID 23687390

Citations 12

Authors

Dika Kuljis

Analyne M Schroeder

Takashi Kudo

Dawn H Loh

David L Willison

Christopher S Colwell

Affiliations

Soon will be listed here.

Abstract

Sleep disorders are common in patients with neurogenerative diseases and manifest early in the disease process. Among a number of possible mechanisms underlying the sleep disturbances, there is evidence that dysfunction in the circadian system is a contributing factor. Focusing on a mouse model of Huntington's disease has enabled us to determine that at the onset of symptoms, spontaneous electrical activity of neurons within the central clock is disrupted even though the molecular clockwork is still functional. These findings suggest that the fundamental deficit contributing to disordered sleep is reduced SCN output. The mechanism underlying this deficit is not yet known, but mitochondrial dysfunction and oxidative stress are likely involved. Disruption of circadian output from the SCN would be expected to have wide ranging impact on the body including SCN regulated brain regions and the heart. In fact, there is a great deal of overlap in the non-motor symptoms experienced by HD patients and the consequences of circadian disruption. This raises the possibility that the disordered sleep and circadian function experienced by HD patients may be an integral part of the disease. Furthermore, we speculate that circadian dysfunction may accelerate the pathology underlying HD. If these hypotheses are correct, we should focus on treating circadian misalignment and sleep disruptions early in disease progression.

Citing Articles

Systemic Symptoms in Huntington's Disease: A Comprehensive Review.

Mehanna R, Jankovic J Mov Disord Clin Pract. 2024; 11(5):453-464.

PMID: 38529740 PMC: 11078495. DOI: 10.1002/mdc3.14029.

The Molecular Clock and Neurodegenerative Disease: A Stressful Time.

Carter B, Justin H, Gulick D, Gamsby J Front Mol Biosci. 2021; 8:644747.

PMID: 33889597 PMC: 8056266. DOI: 10.3389/fmolb.2021.644747.

Do Disruptions in the Circadian Timing System Contribute to Autonomic Dysfunction in Huntington's Disease?.

Park S, Colwell C Yale J Biol Med. 2019; 92(2):291-303.

PMID: 31249490 PMC: 6585531.

Light-exposure at night impairs mouse ovary development via cell apoptosis and DNA damage.

Li Y, Cheng S, Li L, Zhao Y, Shen W, Sun X Biosci Rep. 2019; 39(5).

PMID: 30962269 PMC: 6499499. DOI: 10.1042/BSR20181464.

Pathophysiology in the suprachiasmatic nucleus in mouse models of Huntington's disease.

Kuljis D, Kudo T, Tahara Y, Ghiani C, Colwell C J Neurosci Res. 2018; 96(12):1862-1875.

PMID: 30168855 PMC: 7105277. DOI: 10.1002/jnr.24320.

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