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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1519225/full |
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| Summary: | 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. |
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| ISSN: | 1663-4365 |