Early and progressive circadian abnormalities in Huntington's disease sheep are unmasked by social environment

Morton, A. Jennifer, Rudiger, Skye R., Wood, Nigel I., Sawiak, Stephen J., Brown, Gregory C., McLaughlan, Clive J., Kuchel, Timothy R., Snell, Russell G., Faull, Richard L. M. and Bawden, C. Simon (2014) Early and progressive circadian abnormalities in Huntington's disease sheep are unmasked by social environment. Human Molecular Genetics, 23 13: 3375-3383. doi:10.1093/hmg/ddu047

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Author Morton, A. Jennifer
Rudiger, Skye R.
Wood, Nigel I.
Sawiak, Stephen J.
Brown, Gregory C.
McLaughlan, Clive J.
Kuchel, Timothy R.
Snell, Russell G.
Faull, Richard L. M.
Bawden, C. Simon
Title Early and progressive circadian abnormalities in Huntington's disease sheep are unmasked by social environment
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddu047
Open Access Status Not yet assessed
Volume 23
Issue 13
Start page 3375
End page 3383
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract Insidious changes in behaviour herald the onset of progressive neurodegenerative disorders such as Huntington's disease (HD), sometimes years before overt symptoms are seen. Sleep and circadian disturbances are particularly disruptive symptoms in patients with neurological disorders, but they are difficult to measure in humans. Here we studied circadian behaviour in transgenic HD sheep expressing the full-length human huntingtin protein with an expanded CAG repeat mutation in the juvenile range. Young HD sheep with no other symptoms exhibited circadian behavioural abnormalities that worsened with age. The most obvious change was a disturbed evening behaviour reminiscent of ‘sundowning’ that is seen in some patients with dementia. There were no structural abnormalities seen with magnetic resonance imaging, even in 5-year-old HD sheep. Interestingly, detection of the circadian abnormalities depended upon their social grouping. Abnormalities emerged in sheep kept in an ‘HD-only’ flock, whereas the behaviour of HD sheep kept mixed with normal sheep was relatively normal. Sleep–wake abnormalities in HD patients are also likely to be hidden, and may precede overt symptoms by many years. Sleep disruption has deleterious effects, even in normal people. The knock-on effects of sleep–wake disturbance may exacerbate, or even cause symptoms such as irritability and depression that are common in early stage HD patients. HD sheep will be useful models for probing the mechanisms underlying circadian behavioural disorder in HD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 20 Feb 2014, 00:17:38 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging