Bibliographic Details
| Title: |
Sleep Spindles and Fragmented Sleep as Prodromal Markers in a Preclinical Model of LRRK2-G2019S Parkinson's Disease |
| Authors: |
Lindsey M. Crown, Mitchell J. Bartlett, Jean-Paul L. Wiegand, Allison J. Eby, Emily J. Monroe, Kathleen Gies, Luke Wohlford, Matthew J. Fell, Torsten Falk, Stephen L. Cowen |
| Source: |
Frontiers in Neurology, Vol 11 (2020) |
| Publisher Information: |
Frontiers Media S.A., 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
Parkinson's disease, prodromal, LRRK2, sleep spindles, sleep fragmentation, EEG, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-2295 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fneur.2020.00324/full; https://doaj.org/toc/1664-2295 |
| DOI: |
10.3389/fneur.2020.00324 |
| Access URL: |
https://doaj.org/article/9a9f3bac1f204f1b8953da46c419f8bd |
| Accession Number: |
edsdoj.9a9f3bac1f204f1b8953da46c419f8bd |
| Database: |
Directory of Open Access Journals |
