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

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

Publication date: May 09, 2019

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.

Open Access PDF

Farag’o, A., Zsindely, N., and Bodai, L. Mutant huntingtin disturbs circadian clock gene expression and sleep patterns in Drosophila. 06476. 2019 Sci Rep (9):1.

Concepts Keywords
Circadian Oscillating gene
Circadian Clock Suprachiasmatic nucleus
Circadian Rhythm Timeless
Drosophila Period
Entrainment Cycle
Feedback Loop Circadian clock
Fragmentation Circadian rhythm
Huntingtin Branches of biology
Huntington Deficiency
Pathology Molecular pathology disorder
Sci
Sleep

Semantics

Type Source Name
pathway BSID Reproduction
gene UNIPROT MARK1
gene UNIPROT BRD2
gene UNIPROT CLK1
disease MESH Multiple
disease DOID Huntington disease
disease MESH Huntington disease
pathway BSID Neurodegenerative Diseases
disease DOID sleep disorder
disease MESH sleep disorder
disease MESH cognitive impairment
gene UNIPROT INTU
gene UNIPROT LITAF
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
gene UNIPROT DUOXA1
gene UNIPROT MBNL1
disease DOID Alzheimer Disease
disease MESH Alzheimer Disease
gene UNIPROT PHB2
gene UNIPROT NCR3
gene UNIPROT SGCG
gene UNIPROT LARGE1
gene UNIPROT FANCC
gene UNIPROT OCA2
gene UNIPROT B3GALNT1
drug DRUGBANK Proline
disease MESH **P
gene UNIPROT TPI1
gene UNIPROT HAVCR1
gene UNIPROT ARHGEF5
disease MESH restlessness
gene UNIPROT CTNNBL1
gene UNIPROT MAX
gene UNIPROT MIXL1
gene UNIPROT SLC35G1
gene UNIPROT CHST3
gene UNIPROT NOVA2
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT KCNJ5
gene UNIPROT CIR1
gene UNIPROT ADA2
gene UNIPROT LGALS4
gene UNIPROT SLC6A4
gene UNIPROT ADI1
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT PLPP6
gene UNIPROT PDP1
gene UNIPROT JTB
gene UNIPROT NR1I2
gene UNIPROT CYCS
gene UNIPROT DCLK1
gene UNIPROT HTT
drug DRUGBANK L-Glutamine
disease MESH neurodegenerative disorder
disease MESH depression
disease MESH sleep stages
gene UNIPROT ERBB2
gene UNIPROT NEU1
gene UNIPROT NEURL1
drug DRUGBANK Coenzyme M
gene UNIPROT TIMELESS
disease MESH sleep latency
disease MESH sleep fragmentation
gene UNIPROT CLOCK
gene UNIPROT TNFSF14
pathway BSID Circadian rhythm
disease MESH defects
drug DRUGBANK Tropicamide
pathway BSID Gene Expression
pathway BSID Circadian Clock

Original Article

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