Voluntary wheel running exercise improves sleep disorder, circadian rhythm disturbance, and neuropathology in an animal model of Alzheimer's disease

作者：Yiying Hu, Long Niu, Yixin Chen, Huijia Yang, Xinhui Qiu, Jiang Fei, Cong Liu, Huaibin Cai, Weidong Le · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70314 · 被引用次数：21 · 研究领域：Sleep and Wakefulness Research、Circadian rhythm and melatonin、Sleep and related disorders

INTRODUCTION: The sleep-wake cycle and circadian rhythm disturbances are common in Alzheimer's disease (AD). However, it is not known if exercise has any benefit for the sleep disorders in AD. METHODS: mice). We assessed behavioral circadian rhythm, sleep structure, circadian clock genes, cognitive function, and neurodegeneration in the suprachiasmatic nucleus (SCN), the hippocampus, and the cortex. RESULTS: After VWR exercise in the AD mice, the rapid eye movement sleep was increased by 89%. The levels of circadian clock genes were significantly changed (brain and muscle arnt-like protein 1 [BMAL1] and retinoic acid receptor-related orphan receptorsα [RORα] reduced by 45.7% and 36.4%, reverse erythroblastosis virusα (REV-ERBα) increased by 119%) in the SCN by immunofluorescence staining, with the mRNA levels were markedly altered (Bmal1 and Rorα decreased by 57% and 68%, Rev-erbα elevated by 79%) in the hypothalamus at Zeitgeber Time 1; phospho-tau 231 (p-tau231) was reduced by 35%, whereas vesicular GABA transporter (VGAT) was elevated by 38.7% in the SCN. In addition, ionized calcium binding adapter molecude 1 (Iba1), glial fibrillary acidic protein (GFAP), amyloid β (Aβ), and p-tau231 were significantly reduced in the hippocampus and cortex. DISCUSSION: Our results demonstrate that VWR exercise improves sleep disorders, cognitive deficits, and neuropathology in AD mice. HIGHLIGHTS: Voluntary wheel running (VWR) exercise improves the behavioral circadian rhythm disorder an...