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Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer's disease

Luyan Zhang, Letizia Santoni, Nam Anh Ngo, Reyila SimayiiD, Eleonora FiciaràiD, Luisa de VivoiD, Michele BellesiiD

Abstract

Alzheimers disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and characterized by beta-amyloid plaque and tau tangle pathology. Recent research indicates a bidirectional relationship between AD pathology and sleep disturbances, with disrupted sleep exacerbating AD progression through increased beta-amyloid and tau accumulation. This strongly indicates that improving sleep may exert a direct protective effect on preventing the accumulation and spreading of AD pathology, and possibly slow the cognitive decline. Here we investigated the effects of enhancing sleep via vestibular stimulation (rocking) on AD progression in a 3xTg mouse model. Over a four-month period starting in early adulthood (p60), we monitored sleep patterns, motor function, memory, and AD pathology. Twelve-hour rocking during the light period significantly increased non-rapid eye movement (NREM) sleep duration in mice, although this effect diminished over time due to habituation. Despite this, rocking attenuated motor function decline and reduced beta-amyloid levels in the cerebral cortex of treated mice. No noticeable changes in tau levels were observed following sleep enhancement. In conclusion, our findings highlight the potential of non-pharmacological methods to enhance NREM sleep and modify disease trajectory in AD models, emphasizing the critical role of sleep in neuroprotection.

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