Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease
Sleep disturbances co-occur with and precede the onset of motor symptoms in Parkinson's disease (PD). We evaluated sleep fragmentation and thalamocortical sleep spindles in mice expressing the p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene, one of the most common genetic for...
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doaj-9a9f3bac1f204f1b8953da46c419f8bd2020-11-25T02:18:34ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-05-011110.3389/fneur.2020.00324519148Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's DiseaseLindsey M. Crown0Mitchell J. Bartlett1Mitchell J. Bartlett2Jean-Paul L. Wiegand3Allison J. Eby4Emily J. Monroe5Kathleen Gies6Luke Wohlford7Matthew J. Fell8Torsten Falk9Torsten Falk10Stephen L. Cowen11Stephen L. Cowen12Department of Psychology, University of Arizona, Tucson, AZ, United StatesDepartment of Neurology, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, University of Arizona, Tucson, AZ, United StatesGraduate Interdisciplinary Program in Neuroscience, University of Arizona, Tucson, AZ, United StatesDepartment of Physiology, University of Arizona, Tucson, AZ, United StatesDepartment of Biomedical Engineering, University of Arizona, Tucson, AZ, United StatesDepartment of Psychology, University of Arizona, Tucson, AZ, United StatesCollege of Medicine, University of Arizona, Phoenix, AZ, United StatesMerck & Co., Inc., Boston, MA, United StatesDepartment of Neurology, University of Arizona, Tucson, AZ, United StatesDepartment of Pharmacology, University of Arizona, Tucson, AZ, United StatesDepartment of Psychology, University of Arizona, Tucson, AZ, United StatesGraduate Interdisciplinary Program in Neuroscience, University of Arizona, Tucson, AZ, United StatesSleep disturbances co-occur with and precede the onset of motor symptoms in Parkinson's disease (PD). We evaluated sleep fragmentation and thalamocortical sleep spindles in mice expressing the p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene, one of the most common genetic forms of PD. Thalamocortical sleep spindles are oscillatory events that occur during slow-wave sleep that are involved in memory consolidation. We acquired data from electrocorticography, sleep behavioral measures, and a rotarod-based motor enrichment task in 28 LRRK2-G2019S knock-in mice and 27 wild-type controls (8–10 month-old males). Sleep was more fragmented in LRRK2-G2019S mice; sleep bouts were shorter and more numerous, even though total sleep time was similar to controls. LRRK2-G2019S animals expressed more sleep spindles, and individual spindles were longer in duration than in controls. We then chronically administered the LRRK2-inhibitor MLi-2 in-diet to n = 12 LRRK2-G2019S and n = 15 wild-type mice for a within-subject analysis of the effects of kinase inhibition on sleep behavior and physiology. Treatment with MLi-2 did not impact these measures. The data indicate that the LRRK2-G2019S mutation could lead to reduced sleep quality and altered sleep spindle physiology. This suggests that sleep spindles in LRRK2-G2019S animals could serve as biomarkers for underlying alterations in sleep networks resulting from the LRRK2-G2019S mutation, and further evaluation in human LRRK2-G2019S carriers is therefore warranted.https://www.frontiersin.org/article/10.3389/fneur.2020.00324/fullParkinson's diseaseprodromalLRRK2sleep spindlessleep fragmentationEEG |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lindsey M. Crown Mitchell J. Bartlett Mitchell J. Bartlett Jean-Paul L. Wiegand Allison J. Eby Emily J. Monroe Kathleen Gies Luke Wohlford Matthew J. Fell Torsten Falk Torsten Falk Stephen L. Cowen Stephen L. Cowen |
spellingShingle |
Lindsey M. Crown Mitchell J. Bartlett Mitchell J. Bartlett Jean-Paul L. Wiegand Allison J. Eby Emily J. Monroe Kathleen Gies Luke Wohlford Matthew J. Fell Torsten Falk Torsten Falk Stephen L. Cowen Stephen L. Cowen Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease Frontiers in Neurology Parkinson's disease prodromal LRRK2 sleep spindles sleep fragmentation EEG |
author_facet |
Lindsey M. Crown Mitchell J. Bartlett Mitchell J. Bartlett Jean-Paul L. Wiegand Allison J. Eby Emily J. Monroe Kathleen Gies Luke Wohlford Matthew J. Fell Torsten Falk Torsten Falk Stephen L. Cowen Stephen L. Cowen |
author_sort |
Lindsey M. Crown |
title |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
title_short |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
title_full |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
title_fullStr |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
title_full_unstemmed |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
title_sort |
sleep spindles and fragmented sleep as prodromal markers in a preclinical model of lrrk2-g2019s parkinson's disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2020-05-01 |
description |
Sleep disturbances co-occur with and precede the onset of motor symptoms in Parkinson's disease (PD). We evaluated sleep fragmentation and thalamocortical sleep spindles in mice expressing the p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene, one of the most common genetic forms of PD. Thalamocortical sleep spindles are oscillatory events that occur during slow-wave sleep that are involved in memory consolidation. We acquired data from electrocorticography, sleep behavioral measures, and a rotarod-based motor enrichment task in 28 LRRK2-G2019S knock-in mice and 27 wild-type controls (8–10 month-old males). Sleep was more fragmented in LRRK2-G2019S mice; sleep bouts were shorter and more numerous, even though total sleep time was similar to controls. LRRK2-G2019S animals expressed more sleep spindles, and individual spindles were longer in duration than in controls. We then chronically administered the LRRK2-inhibitor MLi-2 in-diet to n = 12 LRRK2-G2019S and n = 15 wild-type mice for a within-subject analysis of the effects of kinase inhibition on sleep behavior and physiology. Treatment with MLi-2 did not impact these measures. The data indicate that the LRRK2-G2019S mutation could lead to reduced sleep quality and altered sleep spindle physiology. This suggests that sleep spindles in LRRK2-G2019S animals could serve as biomarkers for underlying alterations in sleep networks resulting from the LRRK2-G2019S mutation, and further evaluation in human LRRK2-G2019S carriers is therefore warranted. |
topic |
Parkinson's disease prodromal LRRK2 sleep spindles sleep fragmentation EEG |
url |
https://www.frontiersin.org/article/10.3389/fneur.2020.00324/full |
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