Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease
IntroductionImproving sleep in murine Alzheimer’s disease (AD) is associated with reduced brain amyloidosis. However, the window of opportunity for successful sleep-targeted interventions, regarding the reduction in pathological hallmarks and related cognitive performance, remains poorly characteriz...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1519225/full |
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| author | Sedef Kollarik Sedef Kollarik Sedef Kollarik Dorita Bimbiryte Aakriti Sethi Inês Dias Inês Dias Inês Dias Carlos G. Moreira Daniela Noain Daniela Noain Daniela Noain Daniela Noain |
| author_facet | Sedef Kollarik Sedef Kollarik Sedef Kollarik Dorita Bimbiryte Aakriti Sethi Inês Dias Inês Dias Inês Dias Carlos G. Moreira Daniela Noain Daniela Noain Daniela Noain Daniela Noain |
| author_sort | Sedef Kollarik |
| collection | DOAJ |
| description | IntroductionImproving sleep in murine Alzheimer’s disease (AD) is associated with reduced brain amyloidosis. However, the window of opportunity for successful sleep-targeted interventions, regarding the reduction in pathological hallmarks and related cognitive performance, remains poorly characterized.MethodsHere, we enhanced slow-wave activity (SWA) during sleep via sodium oxybate (SO) oral administration for 2 weeks at early (6 months old) or moderately late (11 months old) disease stages in Tg2576 mice and evaluated resulting neuropathology and behavioral performance.ResultsWe observed that the cognitive performance of 6-month-old Tg2576 mice significantly improved upon SO treatment, whereas no change was observed in 11-month-old mice. Histochemical assessment of amyloid plaques demonstrated that SO-treated 11-month-old Tg2576 mice had significantly less plaque burden than placebo-treated ones, whereas ELISA of insoluble protein fractions from brains of 6-month-old Tg2576 mice indicated lower Aβ-42/Aβ-40 ratio in SO-treated group vs. placebo-treated controls.DiscussionAltogether, our results suggest that SWA-dependent reduction in brain amyloidosis leads to alleviated behavioral impairment in Tg2576 mice only if administered early in the disease course, potentially highlighting the key importance of early sleep-based interventions in clinical cohorts. |
| format | Article |
| id | doaj-art-f65e43b995624c0f95dc0446259212ac |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-f65e43b995624c0f95dc0446259212ac2025-01-03T06:47:24ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-01-011610.3389/fnagi.2024.15192251519225Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s diseaseSedef Kollarik0Sedef Kollarik1Sedef Kollarik2Dorita Bimbiryte3Aakriti Sethi4Inês Dias5Inês Dias6Inês Dias7Carlos G. Moreira8Daniela Noain9Daniela Noain10Daniela Noain11Daniela Noain12Department of Neurology, University Hospital of Zurich, Zurich, SwitzerlandNeuroscience Centre Zurich (ZNZ), Zurich, SwitzerlandUniversity of Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital of Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital of Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital of Zurich, Zurich, SwitzerlandNeuroscience Centre Zurich (ZNZ), Zurich, SwitzerlandD-HEST, ETHZurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital of Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital of Zurich, Zurich, SwitzerlandNeuroscience Centre Zurich (ZNZ), Zurich, SwitzerlandUniversity of Zurich, Zurich, SwitzerlandUniversity Center of Competence Sleep and Health Zurich, University of Zurich, Zurich, SwitzerlandIntroductionImproving sleep in murine Alzheimer’s disease (AD) is associated with reduced brain amyloidosis. However, the window of opportunity for successful sleep-targeted interventions, regarding the reduction in pathological hallmarks and related cognitive performance, remains poorly characterized.MethodsHere, we enhanced slow-wave activity (SWA) during sleep via sodium oxybate (SO) oral administration for 2 weeks at early (6 months old) or moderately late (11 months old) disease stages in Tg2576 mice and evaluated resulting neuropathology and behavioral performance.ResultsWe observed that the cognitive performance of 6-month-old Tg2576 mice significantly improved upon SO treatment, whereas no change was observed in 11-month-old mice. Histochemical assessment of amyloid plaques demonstrated that SO-treated 11-month-old Tg2576 mice had significantly less plaque burden than placebo-treated ones, whereas ELISA of insoluble protein fractions from brains of 6-month-old Tg2576 mice indicated lower Aβ-42/Aβ-40 ratio in SO-treated group vs. placebo-treated controls.DiscussionAltogether, our results suggest that SWA-dependent reduction in brain amyloidosis leads to alleviated behavioral impairment in Tg2576 mice only if administered early in the disease course, potentially highlighting the key importance of early sleep-based interventions in clinical cohorts.https://www.frontiersin.org/articles/10.3389/fnagi.2024.1519225/fullAlzheimer’s diseasesleepmemorymouse modelamyloidosis |
| spellingShingle | Sedef Kollarik Sedef Kollarik Sedef Kollarik Dorita Bimbiryte Aakriti Sethi Inês Dias Inês Dias Inês Dias Carlos G. Moreira Daniela Noain Daniela Noain Daniela Noain Daniela Noain Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease Frontiers in Aging Neuroscience Alzheimer’s disease sleep memory mouse model amyloidosis |
| title | Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease |
| title_full | Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease |
| title_fullStr | Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease |
| title_full_unstemmed | Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease |
| title_short | Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer’s disease |
| title_sort | pharmacological enhancement of slow wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of alzheimer s disease |
| topic | Alzheimer’s disease sleep memory mouse model amyloidosis |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1519225/full |
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