Sleep Physiology Alterations Precede Plethoric Phenotypic Changes in R6/1 Huntington’s Disease Mice.
PLoS ONE. 2015-05-12; 10(5): e0126972
DOI: 10.1371/journal.pone.0126972
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Lebreton F(1), Cayzac S(1), Pietropaolo S(1), Jeantet Y(1), Cho YH(1).
Author information:
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287, Bat B2-Avenue des Facultés, 33405 Talence Cedex, France; Institut de
Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR 5287, Bat
B2-Avenue des Facultés, 33405 Talence Cedex, France.
In hereditary neurodegenerative Huntington’s disease (HD), there exists a
growing consideration that sleep and circadian dysregulations may be important
symptoms. It is not known, however, whether sleep abnormalities contribute to
other behavioral deficits in HD patients and mouse models. To determine the
precise chronology for sleep physiology alterations and other sensory, motor,
psychiatric and cognitive symptoms of HD, the same R6/1 HD transgenics and their
wild-type littermates were recorded monthly for sleep electroencephalogram (EEG)
together with a wide range of behavioral tests according to a longitudinal plan.
We found an early and progressive deterioration of both sleep architecture and
EEG brain rhythms in R6/1 mice, which are correlated timely with their spatial
working memory impairments. Sleep fragmentation and memory impairments were
accompanied by the loss of delta (1-4 Hz) power in the transgenic mice, the
magnitude of which increased with age and disease progression. These precocious
sleep and cognitive impairments were followed by deficits in social behavior,
sensory and motor abilities. Our data confirm the existence and importance of
sleep physiology alterations in the widely used R6/1 mouse line and highlight
their precedence over other plethoric phenotypic changes. The brainwave
abnormalities, may represent a novel biomarker and point to innovative
therapeutic interventions against HD.
Conflict of interest statement: Competing Interests: The authors have declared
that no competing interests exist.