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Early Disruption of Cortical Sleep-Related Oscillations in a Mouse Model of Dementia With Lewy Bodies (DLB) Expressing Human Mutant (A30P) Alpha-Synuclein

Lookup NU author(s): Dr Myrto Stylianou, Dr Boubker Zaaimi, Professor Alan ThomasORCiD, Professor John-Paul TaylorORCiD, Dr Fiona LeBeauORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© Copyright © 2020 Stylianou, Zaaimi, Thomas, Taylor and LeBeau. Changes in sleep behavior and sleep-related cortical activity have been reported in conditions associated with abnormal alpha-synuclein (α-syn) expression, in particular Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Notably, changes can occur in patients years before the onset of cognitive decline. Sleep-related network oscillations play a key role in memory function, but how abnormal α-syn impacts the generation of such activity is currently unclear. To determine whether early changes in sleep-related network activity could also be observed, prior to any previously reported cognitive dysfunction, we used mice that over-express human mutant α-syn (A30P). Recordings in vivo were performed under urethane anesthesia in the medial prefrontal cortex (mPFC) and CA1 region of the hippocampus in young male (2.5 – 4 months old) A30P and age-matched wild type (WT) mice. We found that the slow oscillation (SO) < 1 Hz frequency was significantly faster in both the mPFC and hippocampus in A30P mice, and Up-state-associated fast oscillations at beta (20 – 30 Hz) and gamma (30 – 80 Hz) frequencies were delayed relative to the onset of the Up-state. Spindle (8 – 15 Hz) activity in the mPFC was also altered in A30P mice, as spindles were shorter in duration and had reduced density compared to WT. These changes demonstrate that dysregulation of sleep-related oscillations occurs in young A30P mice long before the onset of cognitive dysfunction. Our data suggest that, as seen in patients, changes in sleep-related oscillations are an early consequence of abnormal α-syn aggregation in A30P mice.

Publication metadata

Author(s): Stylianou M, Zaaimi B, Thomas A, Taylor J-P, LeBeau FEN

Publication type: Article

Publication status: Published

Journal: Frontiers in Neuroscience

Year: 2020

Volume: 14

Online publication date: 17/09/2020

Acceptance date: 25/08/2020

Date deposited: 19/11/2020

ISSN (print): 1662-4548

ISSN (electronic): 1662-453X

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fnins.2020.579867

DOI: 10.3389/fnins.2020.579867

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