Zolpidem restores sleep and decreases amyloid in a mouse model

TL;DR

Zolpidem improves sleep and reduces amyloid in a mouse model of Alzheimer's disease, suggesting potential early-stage therapeutic benefits.

Contribution

Zolpidem is shown to restore sleep rhythms and reduce amyloid plaque burden in a mouse model of Alzheimer's disease.

Findings

Zolpidem restored NREM sleep and rescued slow oscillation brain rhythms in APP/PS1 mice.

Zolpidem reduced cortical amyloid plaque burden and neuronal calcium overload.

Zolpidem improved sleep-dependent memory consolidation without affecting locomotion.

Abstract

Deficits in non–rapid eye movement (NREM) sleep facilitate Alzheimer's disease (AD) progression. Enhancing gamma‐aminobutyric acid‐ergic (GABAergic) signaling can restore sleep. Unbiased computational analysis identified zolpidem as high‐affinity GABA receptor modulator facilitating chloride transport that could slow AD.

Zolpidem's effects on sleep and Alzheimer's progression were evaluated in young APP/PS1 (amyloid precursor protein/presenilin 1) mice. Sleep was monitored with electroencephalography/electromyography (EEG/EMG) telemetry. Wide‐field imaging with voltage‐sensitive dyes (VSDs) was used to track sleep‐dependent brain rhythms. Multiphoton microscopy allowed assessments of amyloid plaque load and basal neuronal calcium levels. Behavioral assays were used to measure memory and cognitive function.

Zolpidem restored NREM sleep and rescued sleep‐dependent brain rhythm, slow oscillation. Zolpidem administration reduced cortical amyloid plaque burden, mitigated neuronal calcium overload, and enhanced sleep‐dependent contextual recall without adverse effects on locomotion.

Zolpidem effectively decreased amyloid in young APP/PS1 mice. This supports zolpidem's therapeutic promise as an intervention strategy at early stages of AD.

Zolpidem treatment improves non–rapid eye movement (NREM) sleep stability and reduces sleep fragmentation.Zolpidem restores slow oscillation in young APP/PS1 (amyloid precursor protein/presenilin 1) mice.Zolpidem treatment reduces amyloid plaque burden and calcium overload in neurons.Zolpidem‐treated mice show improved sleep‐dependent memory consolidation.Sleep rhythm enhancement shows promise for Alzheimer's therapy.

Zolpidem treatment improves non–rapid eye movement (NREM) sleep stability and reduces sleep fragmentation.

Zolpidem restores slow oscillation in young APP/PS1 (amyloid precursor protein/presenilin 1) mice.

Zolpidem treatment reduces amyloid plaque burden and calcium overload in neurons.

Zolpidem‐treated mice show improved sleep‐dependent memory consolidation.

Sleep rhythm enhancement shows promise for Alzheimer's therapy.

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