Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila
Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging...
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ftoregonstate:ir.library.oregonstate.edu:nz806147j 2024-04-14T08:08:19+00:00 Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila Long, Dani M. Blake, Matthew R. Dutta, Sudeshna Holbrook, Scott D. Kotwica-Rolinska, Joanna Kretzschmar, Doris Giebultowicz, Jadwiga M. https://ir.library.oregonstate.edu/concern/articles/nz806147j English [eng] eng unknown Public Library of Science https://ir.library.oregonstate.edu/concern/articles/nz806147j In Copyright Article ftoregonstate 2024-03-21T15:49:07Z Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer’s disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per[superscript 01]). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism. Article in Journal/Newspaper Arctic ScholarsArchive@OSU (Oregon State University) Arctic |
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Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer’s disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per[superscript 01]). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism. |
format |
Article in Journal/Newspaper |
author |
Long, Dani M. Blake, Matthew R. Dutta, Sudeshna Holbrook, Scott D. Kotwica-Rolinska, Joanna Kretzschmar, Doris Giebultowicz, Jadwiga M. |
spellingShingle |
Long, Dani M. Blake, Matthew R. Dutta, Sudeshna Holbrook, Scott D. Kotwica-Rolinska, Joanna Kretzschmar, Doris Giebultowicz, Jadwiga M. Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
author_facet |
Long, Dani M. Blake, Matthew R. Dutta, Sudeshna Holbrook, Scott D. Kotwica-Rolinska, Joanna Kretzschmar, Doris Giebultowicz, Jadwiga M. |
author_sort |
Long, Dani M. |
title |
Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
title_short |
Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
title_full |
Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
title_fullStr |
Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
title_full_unstemmed |
Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila |
title_sort |
relationships between the circadian system and alzheimer’s disease-like symptoms in drosophila |
publisher |
Public Library of Science |
url |
https://ir.library.oregonstate.edu/concern/articles/nz806147j |
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Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
https://ir.library.oregonstate.edu/concern/articles/nz806147j |
op_rights |
In Copyright |
_version_ |
1796305752894210048 |