Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease
AuthorCrown, Lindsey M
Bartlett, Mitchell J
Wiegand, Jean-Paul L
Eby, Allison J
Monroe, Emily J
Fell, Matthew J
Cowen, Stephen L
AffiliationUniv Arizona, Dept Psychol
Univ Arizona, Dept Neurol
Univ Arizona, Dept Pharmacol
Univ Arizona, Grad Interdisciplinary Program Neurosci
Univ Arizona, Dept Physiol
Univ Arizona, Dept Biomed Engn
Univ Arizona, Coll Med
MetadataShow full item record
PublisherFRONTIERS MEDIA SA
CitationCrown, L. M., Bartlett, M. J., Wiegand, J. P. L., Eby, A. J., Monroe, E. J., Gies, K., ... & Cowen, S. L. (2020). Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease. Frontiers in Neurology, 11, 324.
JournalFRONTIERS IN NEUROLOGY
RightsCopyright © 2020 Crown, Bartlett, Wiegand, Eby, Monroe, Gies, Wohlford, Fell, Falk and Cowen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s)are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractSleep 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.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as Copyright © 2020 Crown, Bartlett, Wiegand, Eby, Monroe, Gies, Wohlford, Fell, Falk and Cowen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s)are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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