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Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein
BACKGROUND: Sleep disruptions occur early and frequently in Parkinson’s disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777499/ https://www.ncbi.nlm.nih.gov/pubmed/24867919 http://dx.doi.org/10.3233/JPD-140374 |
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author | McDowell, Kimberly A. Shin, David Roos, Kenneth P. Chesselet, Marie-Françoise |
author_facet | McDowell, Kimberly A. Shin, David Roos, Kenneth P. Chesselet, Marie-Françoise |
author_sort | McDowell, Kimberly A. |
collection | PubMed |
description | BACKGROUND: Sleep disruptions occur early and frequently in Parkinson’s disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models. OBJECTIVE: The objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model. METHODS: At 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype. RESULTS: Thy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness. CONCLUSIONS: Alpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD. |
format | Online Article Text |
id | pubmed-5777499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57774992018-01-29 Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein McDowell, Kimberly A. Shin, David Roos, Kenneth P. Chesselet, Marie-Françoise J Parkinsons Dis Research Report BACKGROUND: Sleep disruptions occur early and frequently in Parkinson’s disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models. OBJECTIVE: The objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model. METHODS: At 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype. RESULTS: Thy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness. CONCLUSIONS: Alpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD. IOS Press 2018-01-10 /pmc/articles/PMC5777499/ /pubmed/24867919 http://dx.doi.org/10.3233/JPD-140374 Text en © 2014 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report McDowell, Kimberly A. Shin, David Roos, Kenneth P. Chesselet, Marie-Françoise Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title | Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title_full | Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title_fullStr | Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title_full_unstemmed | Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title_short | Sleep Dysfunction and EEG Alterations in Mice Overexpressing Alpha-Synuclein |
title_sort | sleep dysfunction and eeg alterations in mice overexpressing alpha-synuclein |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777499/ https://www.ncbi.nlm.nih.gov/pubmed/24867919 http://dx.doi.org/10.3233/JPD-140374 |
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