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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2023

Open Access 01-12-2023 | Alzheimer's Disease | Research

Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats

Authors: Audrey Hector, Chloé Provost, Benoît Delignat-Lavaud, Khadija Bouamira, Chahinez-Anissa Menaouar, Valérie Mongrain, Jonathan Brouillette

Published in: Alzheimer's Research & Therapy | Issue 1/2023

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Abstract

Background

Soluble amyloid-beta oligomers (Aβo) begin to accumulate in the human brain one to two decades before a clinical diagnosis of Alzheimer’s disease (AD). The literature supports that soluble Aβo are implicated in synapse and neuronal losses in the brain regions such as the hippocampus. This region importantly contributes to explicit memory, the first type of memory affected in AD. During AD preclinical and prodromal stages, people are also experiencing wake/sleep alterations such as insomnia (e.g., difficulty initiating sleep, decreased sleep duration), excessive daytime sleepiness, and sleep schedule modifications. In addition, changes in electroencephalographic (EEG) activity during wake and sleep have been reported in AD patients and animal models. However, the specific contribution of Aβo to wake/sleep alterations is poorly understood and was investigated in the present study.

Methods

Chronic hippocampal injections of soluble Aβo were conducted in male rats and combined with EEG recording to determine the progressive impact of Aβ pathology specifically on wake/sleep architecture and EEG activity. Bilateral injections were conducted for 6 consecutive days, and EEG acquisition was done before, during, and after Aβo injections. Immunohistochemistry was used to assess neuron numbers in the hippocampal dentate gyrus (DG).

Results

Aβo injections did not affect the time spent in wakefulness, slow wave sleep (SWS), and paradoxical sleep but altered EEG activity during wake and SWS. More precisely, Aβo increased slow-wave activity (SWA; 0.5–5 Hz) and low-beta activity (16–20 Hz) during wake and decreased theta (5–9 Hz) and alpha (9–12 Hz) activities during SWS. Moreover, the theta activity/SWA ratio during wake and SWS was decreased by Aβo. These effects were significant only after 6 days of Aβo injections and were found with alterations in neuron counts in the DG.

Conclusions

We found multiple modifications of the wake and SWS EEG following Aβo delivery to the hippocampus. These findings expose a specific EEG signature of Aβ pathology and can serve the development of non-invasive and cost-effective markers for the early diagnosis of AD or other amyloid-related diseases.
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Metadata
Title
Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats
Authors
Audrey Hector
Chloé Provost
Benoît Delignat-Lavaud
Khadija Bouamira
Chahinez-Anissa Menaouar
Valérie Mongrain
Jonathan Brouillette
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-023-01316-4

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