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Scientific article
Open access
English

Sleep Physiology Alterations Precede Plethoric Phenotypic Changes in R6/1 Huntington's Disease Mice

Published inPLOS ONE, vol. 10, no. 5, e0126972
Publication date2015
Abstract

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.

Keywords
  • Animals
  • Brain/physiopathology
  • Circadian Rhythm
  • Disease Models, Animal
  • Disease Progression
  • Electroencephalography
  • Huntingtin Protein
  • Huntington Disease/complications/physiopathology/psychology
  • Male
  • Mice
  • Motor Activity/physiology
  • Nerve Tissue Proteins/genetics
  • Nuclear Proteins/genetics
  • Sleep Deprivation/physiopathology
Affiliation Not a UNIGE publication
Citation (ISO format)
LEBRETON, Fanny et al. Sleep Physiology Alterations Precede Plethoric Phenotypic Changes in R6/1 Huntington’s Disease Mice. In: PLOS ONE, 2015, vol. 10, n° 5, p. e0126972. doi: 10.1371/journal.pone.0126972
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Article (Published version)
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ISSN of the journal1932-6203
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