Circadian dysfunction in a mouse model of Parkinson's disease.

TitleCircadian dysfunction in a mouse model of Parkinson's disease.
Publication TypeJournal Article
Year of Publication2011
AuthorsKudo, T, Loh DH, Truong D, Wu Y, Colwell CS
JournalExperimental neurology
Volume232
Issue1
Pagination66-75
Date Published2011 Nov
ISSN1090-2430
KeywordsAging, alpha-Synuclein, Animals, Cell Count, Circadian Rhythm, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Motor Activity, Parkinson Disease, Period Circadian Proteins, Suprachiasmatic Nucleus
Abstract

Many Parkinson's disease (PD) patients exhibit sleep disorders as part of their symptoms with evidence suggesting that REM sleep disorders may be intimately associated with this disease. Possible dysfunction in the circadian system in PD has received less attention, yet problems in circadian timing are common in neurodegenerative diseases. In the present study, we examined the expression of daily and circadian rhythms in the alpha-synuclein overexpressing (ASO) transgenic line. We found selective deficits in the expression of circadian rhythms of locomotor activity, including lower night-time activity and greater fragmentation in the wheel-running activity in this PD model. These alterations were prominent in young adult (3-4 mo) ASO mice and worsened progressively with age, consistent with prior reports of age-related loss of motor skills. The temporal distribution of sleep was also altered in the ASO mice compared to littermate controls. In the ASO mice, the peak/trough expression of the clock gene PERIOD2 was normal in the master pacemaker of the circadian system: the suprachiasmatic nucleus (SCN); however, the daytime firing rate of SCN neurons was reduced in the mutant mice. Together, this data raises the possibility that a weakening of circadian output is a core feature of PD. The reduction in magnitude of circadian output would be expected to have functional consequences throughout the body.

DOI10.1111/j.1460-9568.2012.08054.x
Alternate JournalExp. Neurol.