Acoustic Stimulation Improves Memory and Reverses the Contribution of Chronic Sleep Deprivation to Pathology in 3xTgAD Mice

Abstract

Acoustic stimulation during sleep is believed to enhance slow waves, which are critical to memory consolidation. However, clinical trials of acoustic stimulation have yielded mixed results concerning its effectiveness in improving human memory. A few studies have implied that acoustic stimulation ameliorates the pathology of Alzheimer's disease (AD) in mice with normal sleep. Here, we explored the effect of acoustic stimulation on 3xTgAD mice suffering from chronic sleep deprivation, as these data may shed light on the potential use of acoustic stimulation in AD patients with insomnia. Methods: Twenty-four 8-month-old 3xTgAD mice were randomly and equally divided into three groups: the normal sleep group (S group), the sleep deprivation group (SD group), and the acoustic stimulation group (AS group). During a 14-day sleep intervention, the SD and AS groups received 6 h of sleep deprivation per day, and the AS group also received acoustic stimulation in the dark phase. Then, the mice underwent Morris water maze (MWM) tests and arterial spin labelling (ASL) magnetic resonance imaging (MRI) scans and were sacrificed for pathological evaluation. Results: The three groups showed similar stress levels. The S and AS groups exhibited better spatial memory, better brain perfusion, and milder amyloid β (Aβ) and tau pathology than the SD group, although no significant discrepancies were found between the S and AS groups. Conclusion: Acoustic stimulation may exert a protective effect in 3xTgAD mice by improving spatial memory, enhancing the blood supply of the brain, and reversing the contribution of chronic sleep deprivation to Aβ and tau pathology to mimic the effect of normal sleep patterns.