Sleep inhibition induced by amyloid-β oligomers is mediated by the cellular prion protein
© 2020 European Sleep Research Society..
Sleep is severely impaired in patients with Alzheimer's disease. Amyloid-β deposition in the brain of Alzheimer's disease patients is a key event in its pathogenesis and is associated with disrupted sleep, even before the appearance of cognitive decline. Because soluble amyloid-β oligomers are the key mediators of synaptic and cognitive dysfunction in Alzheimer's disease and impair long-term memory in rodents, the first aim of this study was to test the hypothesis that amyloid-β oligomers would directly impair sleep in mice. The cellular prion protein is a cell surface glycoprotein of uncertain function. Because cellular prion protein binds oligomeric amyloid-β with high affinity and mediates some of its neurotoxic effects, the second aim of the study was to test whether amyloid-β oligomer-induced sleep alterations were mediated by cellular prion protein. To address these aims, wild-type and cellular prion protein-deficient mice were given acute intracerebroventricular injections (on different days, at lights on) of vehicle and synthetic amyloid-β oligomers. Compared to vehicle, amyloid-β oligomers significantly reduced the amount of time spent in non-rapid eye movement sleep by wild-type mice during both the light and dark phases of the light-dark cycle. The amount of time spent in rapid eye movement sleep was reduced during the dark phase. Sleep was also fragmented by amyloid-β oligomers, as the number of transitions between states increased in post-injection hours 9-24. No such effects were observed in cellular prion protein-deficient mice. These results show that amyloid-β oligomers do inhibit and fragment sleep, and that these effects are mediated by cellular prion protein.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Journal of sleep research - 30(2021), 3 vom: 26. Juni, Seite e13187 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Del Gallo, Federico [VerfasserIn] |
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| Links: |
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| Themen: |
Aβ oligomers |
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| Anmerkungen: |
Date Completed 14.07.2021 Date Revised 14.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jsr.13187 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Sleep is severely impaired in patients with Alzheimer's disease. Amyloid-β deposition in the brain of Alzheimer's disease patients is a key event in its pathogenesis and is associated with disrupted sleep, even before the appearance of cognitive decline. Because soluble amyloid-β oligomers are the key mediators of synaptic and cognitive dysfunction in Alzheimer's disease and impair long-term memory in rodents, the first aim of this study was to test the hypothesis that amyloid-β oligomers would directly impair sleep in mice. The cellular prion protein is a cell surface glycoprotein of uncertain function. Because cellular prion protein binds oligomeric amyloid-β with high affinity and mediates some of its neurotoxic effects, the second aim of the study was to test whether amyloid-β oligomer-induced sleep alterations were mediated by cellular prion protein. To address these aims, wild-type and cellular prion protein-deficient mice were given acute intracerebroventricular injections (on different days, at lights on) of vehicle and synthetic amyloid-β oligomers. Compared to vehicle, amyloid-β oligomers significantly reduced the amount of time spent in non-rapid eye movement sleep by wild-type mice during both the light and dark phases of the light-dark cycle. The amount of time spent in rapid eye movement sleep was reduced during the dark phase. Sleep was also fragmented by amyloid-β oligomers, as the number of transitions between states increased in post-injection hours 9-24. No such effects were observed in cellular prion protein-deficient mice. These results show that amyloid-β oligomers do inhibit and fragment sleep, and that these effects are mediated by cellular prion protein | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a Aβ oligomers | |
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| 700 | 1 | |a Bianchi, Susanna |e verfasserin |4 aut | |
| 700 | 1 | |a Bertani, Ilaria |e verfasserin |4 aut | |
| 700 | 1 | |a Messa, Massimo |e verfasserin |4 aut | |
| 700 | 1 | |a Colombo, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Balducci, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Salmona, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Imeri, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Chiesa, Roberto |e verfasserin |4 aut | |
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