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The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer’s disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We fi...

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Autores principales: Chen, Ko-Fan, Possidente, Bernard, Lomas, David A., Crowther, Damian C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974455/
https://www.ncbi.nlm.nih.gov/pubmed/24574361
http://dx.doi.org/10.1242/dmm.014134
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author Chen, Ko-Fan
Possidente, Bernard
Lomas, David A.
Crowther, Damian C.
author_facet Chen, Ko-Fan
Possidente, Bernard
Lomas, David A.
Crowther, Damian C.
author_sort Chen, Ko-Fan
collection PubMed
description Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer’s disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons. Even in the absence of any behavioural correlate, the synchronised activity of the central clock remains protective, prolonging lifespan, in Aβ flies just as it does in control flies. Confocal microscopy and bioluminescence measurements point to processes downstream of the molecular clock as the main site of Aβ toxicity. In addition, there seems to be significant non-cell-autonomous Aβ toxicity resulting in morphological and probably functional signalling deficits in central clock neurons.
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spelling pubmed-39744552014-04-04 The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease Chen, Ko-Fan Possidente, Bernard Lomas, David A. Crowther, Damian C. Dis Model Mech Research Articles Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer’s disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons. Even in the absence of any behavioural correlate, the synchronised activity of the central clock remains protective, prolonging lifespan, in Aβ flies just as it does in control flies. Confocal microscopy and bioluminescence measurements point to processes downstream of the molecular clock as the main site of Aβ toxicity. In addition, there seems to be significant non-cell-autonomous Aβ toxicity resulting in morphological and probably functional signalling deficits in central clock neurons. The Company of Biologists Limited 2014-04 2014-02-26 /pmc/articles/PMC3974455/ /pubmed/24574361 http://dx.doi.org/10.1242/dmm.014134 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Articles
Chen, Ko-Fan
Possidente, Bernard
Lomas, David A.
Crowther, Damian C.
The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title_full The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title_fullStr The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title_full_unstemmed The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title_short The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease
title_sort central molecular clock is robust in the face of behavioural arrhythmia in a drosophila model of alzheimer’s disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974455/
https://www.ncbi.nlm.nih.gov/pubmed/24574361
http://dx.doi.org/10.1242/dmm.014134
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