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Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease
BACKGROUND: Clinical observations reveal that rapid eye movement (REM) sleep behavior disorder (RBD) often develops prior to alpha-synucleinopathies including Parkinson’s disease (PD). However, a causal relationship between alpha-synucleinopathy and Parkinsonian neurodegeneration has not been deline...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502064/ https://www.ncbi.nlm.nih.gov/pubmed/34675721 http://dx.doi.org/10.2147/NSS.S328365 |
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author | Du, Lida Xu, Linhao Liang, Tuo Wing, Yun-Kwok Ke, Ya Yung, Wing-Ho |
author_facet | Du, Lida Xu, Linhao Liang, Tuo Wing, Yun-Kwok Ke, Ya Yung, Wing-Ho |
author_sort | Du, Lida |
collection | PubMed |
description | BACKGROUND: Clinical observations reveal that rapid eye movement (REM) sleep behavior disorder (RBD) often develops prior to alpha-synucleinopathies including Parkinson’s disease (PD). However, a causal relationship between alpha-synucleinopathy and Parkinsonian neurodegeneration has not been delineated. METHODS: Rats were chronically treated with rotenone and EEG and EMG signals were recorded for analysis of sleep behavior, assisted by video recording of body movements. C-fos expression and TUNEL staining were used to assess neuronal activation and apoptosis, respectively. Chemogenetic manipulation of brain stem nuclei was conducted to ameliorate RBD symptoms in rotenone-treated rats. RESULTS: Rats chronically exposed to rotenone exhibited progressive RBD features, from EEG slowing to REM sleep motor behavior and NREM muscle activities. Temporally, these phenomena correlated well with progressive alpha-synuclein aggregation and neuronal apoptosis in the sublaterodorsal tegmental nucleus (SLD) and gigantocellular ventricular reticular nucleus in the brainstem. Chemogenetic activation of glutamatergic neurons in SLD alleviated RBD symptoms in the rotenone model. CONCLUSION: Taken together, these results are consistent with a progressive degeneration in the REM sleep promoting and atonia circuit in early Parkinsonism that underlies the emergence of RBD symptoms, and demonstrate that the rotenone model is useful for further studies into RBD and its relationship to PD. |
format | Online Article Text |
id | pubmed-8502064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-85020642021-10-20 Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease Du, Lida Xu, Linhao Liang, Tuo Wing, Yun-Kwok Ke, Ya Yung, Wing-Ho Nat Sci Sleep Original Research BACKGROUND: Clinical observations reveal that rapid eye movement (REM) sleep behavior disorder (RBD) often develops prior to alpha-synucleinopathies including Parkinson’s disease (PD). However, a causal relationship between alpha-synucleinopathy and Parkinsonian neurodegeneration has not been delineated. METHODS: Rats were chronically treated with rotenone and EEG and EMG signals were recorded for analysis of sleep behavior, assisted by video recording of body movements. C-fos expression and TUNEL staining were used to assess neuronal activation and apoptosis, respectively. Chemogenetic manipulation of brain stem nuclei was conducted to ameliorate RBD symptoms in rotenone-treated rats. RESULTS: Rats chronically exposed to rotenone exhibited progressive RBD features, from EEG slowing to REM sleep motor behavior and NREM muscle activities. Temporally, these phenomena correlated well with progressive alpha-synuclein aggregation and neuronal apoptosis in the sublaterodorsal tegmental nucleus (SLD) and gigantocellular ventricular reticular nucleus in the brainstem. Chemogenetic activation of glutamatergic neurons in SLD alleviated RBD symptoms in the rotenone model. CONCLUSION: Taken together, these results are consistent with a progressive degeneration in the REM sleep promoting and atonia circuit in early Parkinsonism that underlies the emergence of RBD symptoms, and demonstrate that the rotenone model is useful for further studies into RBD and its relationship to PD. Dove 2021-10-05 /pmc/articles/PMC8502064/ /pubmed/34675721 http://dx.doi.org/10.2147/NSS.S328365 Text en © 2021 Du et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Du, Lida Xu, Linhao Liang, Tuo Wing, Yun-Kwok Ke, Ya Yung, Wing-Ho Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title | Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title_full | Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title_fullStr | Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title_full_unstemmed | Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title_short | Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson’s Disease |
title_sort | progressive pontine-medullary dysfunction leads to rem sleep behavior disorder symptoms in a chronic model of parkinson’s disease |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502064/ https://www.ncbi.nlm.nih.gov/pubmed/34675721 http://dx.doi.org/10.2147/NSS.S328365 |
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