Mutant huntingtin disturbs circadian clock gene expression and sleep patterns in Drosophila

• Published in: Scientific reports Vol. 9; no. 1; p. 7174
• Main Authors: Faragó, Anikó, Zsindely, Nóra, Bodai, László
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.05.2019; Nature Publishing Group
• Subjects: 13/56; 38/77; 631/208/200; 631/378/1385/2640; 631/378/1689/1558; 64/24; Animals; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; Circadian Clocks - genetics; Circadian rhythm; Circadian rhythms; Clock gene; Defects; Disease Models, Animal; Drosophila; Drosophila - genetics; Drosophila - physiology; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Entrainment; Feedback; Gene expression; Gene Expression Regulation; Humanities and Social Sciences; Huntingtin; Huntingtin Protein - deficiency; Huntingtin Protein - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Huntington's disease; Insects; Latency; multidisciplinary; Phenotype; Science; Science (multidisciplinary); Sleep; Sleep - genetics; Sleep - physiology; Sleep and wakefulness; Timeless protein; Transcription; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43612-w

Deficiency of the sleep-wake cycle can accelerate the progression of Huntington’s disease (HD) and exacerbate symptoms making it a target of investigation to better understand the molecular pathology of the disorder. In this study we analyzed sleep defects in a Drosophila model of HD and investigated whether disturbed sleep coincides with alterations in the molecular mechanism controlling circadian rhythm. To analyze sleep defects we recorded the daily activity of flies in 12:12 hours light:dark entrainment and in regard to the underlying molecular mechanism measured circadian “clock” gene expression. In HD flies we observed reduced amount of sleep, sleep fragmentation and prolonged sleep latency. We found changes in gene expression patterns of both transcriptional feedback loops of circadian regulation. We detected prolonged expression of the core feedback loop components period and timeless , whilst the secondary feedback loop member vrille had lower expression rates in general. Our results show that the Drosophila HD model recapitulates most of the sleep related symptoms reported in patients therefore it can be a potential tool to study the molecular background of sleep defects in HD. Altered expression of circadian “clock” genes suggests that disturbed sleep pattern in HD might be the consequence of disturbed circadian regulation.