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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2014
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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. |
format | Online Article Text |
id | pubmed-3974455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
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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