Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats
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 hippocam...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-023-01316-4 |
| _version_ | 1797453599062622208 |
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| author | Audrey Hector Chloé Provost Benoît Delignat-Lavaud Khadija Bouamira Chahinez-Anissa Menaouar Valérie Mongrain Jonathan Brouillette |
| author_facet | Audrey Hector Chloé Provost Benoît Delignat-Lavaud Khadija Bouamira Chahinez-Anissa Menaouar Valérie Mongrain Jonathan Brouillette |
| author_sort | Audrey Hector |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:25:08Z |
| format | Article |
| id | doaj.art-2f6417eed4e74d12ba15182bc635bb6b |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-03-09T15:25:08Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-2f6417eed4e74d12ba15182bc635bb6b2023-11-26T12:32:59ZengBMCAlzheimer’s Research & Therapy1758-91932023-10-0115111410.1186/s13195-023-01316-4Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in ratsAudrey Hector0Chloé Provost1Benoît Delignat-Lavaud2Khadija Bouamira3Chahinez-Anissa Menaouar4Valérie Mongrain5Jonathan Brouillette6Department of Pharmacology and Physiology, Université de MontréalCenter for Advanced Research in Sleep Medicine, CIUSSS-NIMCenter for Advanced Research in Sleep Medicine, CIUSSS-NIMCenter for Advanced Research in Sleep Medicine, CIUSSS-NIMCenter for Advanced Research in Sleep Medicine, CIUSSS-NIMCenter for Advanced Research in Sleep Medicine, CIUSSS-NIMDepartment of Pharmacology and Physiology, Université de MontréalAbstract 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.https://doi.org/10.1186/s13195-023-01316-4Alzheimer’s disease (AD)Pathological markersHippocampusSleep architectureSleep durationEEG spectral analysis |
| spellingShingle | Audrey Hector Chloé Provost Benoît Delignat-Lavaud Khadija Bouamira Chahinez-Anissa Menaouar Valérie Mongrain Jonathan Brouillette Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats Alzheimer’s Research & Therapy Alzheimer’s disease (AD) Pathological markers Hippocampus Sleep architecture Sleep duration EEG spectral analysis |
| title | Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats |
| title_full | Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats |
| title_fullStr | Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats |
| title_full_unstemmed | Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats |
| title_short | Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats |
| title_sort | hippocampal injections of soluble amyloid beta oligomers alter electroencephalographic activity during wake and slow wave sleep in rats |
| topic | Alzheimer’s disease (AD) Pathological markers Hippocampus Sleep architecture Sleep duration EEG spectral analysis |
| url | https://doi.org/10.1186/s13195-023-01316-4 |
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