マウスにおける神経過活動およびミクログリア活性化の阻害による睡眠構築および恒常的回復の調節におけるケルセチン

Quercetin is a naturally occurring flavonoid widely distributed in plants that exhibits various biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. It exhibits a potential role in sleep regulation and homeostasis; however, its specific effects on sleep-wake cycles and underlying mechanisms remain unelucidated.

To systematically investigate the regulatory role of quercetin in sleep architecture and homeostatic recovery, polysomnography (PSG) was used to monitor sleep parameters in mice under normal circadian rhythms and acute sleep deprivation (ASD). Immunofluorescence staining was performed to assess the expression of cellular proto-oncogene protein Fos (c-Fos) and microglial activation in sleep-related brain regions, including the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), paraventricular thalamic nucleus (PVT), hippocampal dentate gyrus (DG), basolateral amygdala (BLA), and periaqueductal gray (PAG).

Under normal circadian conditions, high-dose quercetin promoted non-rapid eye movement (NREM) sleep in mice. In ASD models, quercetin enhanced NREM sleep rebound during the early recovery phase. It sustained higher levels of wakefulness during the subsequent light phase, exhibiting its dual role in accelerating homeostatic recovery while balancing circadian arousal. Immunofluorescence analyses showed that quercetin markedly suppressed c-Fos expression in the mPFC, BLA, and PVT under sleep-deprived conditions. Additionally, it inhibited microglial activation in the mPFC and NAc.

These results mechanistically associate the sleep-regulatory effects of quercetin with its dual inhibition of neuronal hyperactivity in sleep-associated brain regions and neuroinflammatory responses. Altogether, this study identifies quercetin as a novel natural modulator of sleep homeostasis, underscoring its therapeutic potential for sleep disorders via anti-excitatory and anti-inflammatory mechanisms.