Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease
Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease
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DOI：
10.1016/j.cmet.2023.07.014
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发表时间：
2023-10-03
期刊：
影响因子：
29
通讯作者：
Desplats，Paula
中科院分区：
文献类型：
--
作者：
Whittaker，Daniel S.;Akhmetova，Laila;Desplats，Paula
昼夜节律紊乱影响几乎所有阿尔茨海默病（AD）患者，强调其在病理学中的潜在作用以及研究昼夜节律调节干预的治疗潜力的迫切需要。在这里，我们表明，时间限制喂养（TRF）没有热量限制改善关键疾病的组成部分，包括行为的时间，疾病病理，海马转录和记忆在两个转基因（TG）小鼠模型的AD。我们发现，TRF具有同时减少淀粉样蛋白沉积、增加Aβ42清除、改善睡眠和记忆以及使多个基因（包括与AD和神经炎症相关的基因）的日常转录模式正常化的显著能力。因此，我们的研究首次揭示了定时喂养对AD的多效性，这不仅对新陈代谢有深远的影响，还改善了神经退行性变和昼夜节律的失调。由于TRF可以显著改变疾病轨迹，因此这种干预具有立即转化的潜力，解决了对减少或阻止AD进展的可获得方法的迫切需求。
Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.