美国加州大学Paula Desplats课题组在研究中取得进展。他们发现通过限时喂养（TRF）调节昼夜节律可挽救阿尔茨海默病（AD）模型小鼠大脑的病理特征并改善记忆力。这一研究成果发表在2023年8月21日出版的国际学术期刊《细胞-代谢》上。

研究人员表明，无热量限制的限时喂养改善了两个转基因（TG）AD模型小鼠的关键病理特征，包括行为时间、疾病病理学、海马转录和记忆。研究发现TRF同时具有减少淀粉样蛋白沉积、增加Aβ42清除率、改善睡眠和记忆力以及使多个基因（包括与AD和神经炎症相关的基因）转录模式正常化的显著能力。

因此，该研究首次揭示了限时进食对AD的多效性，其影响超过了新陈代谢，改善了神经变性和昼夜节律的错位。由于TRF可以明显改变疾病轨迹，这种干预具有直接的转化潜力，满足了对减少或阻止AD进展可及方法的迫切需求。

研究人员表示，昼夜节律紊乱几乎影响了所有阿尔茨海默病患者，突出了节律在病理学中的潜在作用以及干扰昼夜节律作为潜在治疗措施的必要性。

附：英文原文

Title: Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease

Author: Daniel S. Whittaker, Laila Akhmetova, Daniel Carlin, Haylie Romero, David K. Welsh, Christopher S. Colwell, Paula Desplats

Issue&Volume: 2023-08-21

Abstract: 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.

DOI: 10.1016/j.cmet.2023.07.014

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00273-5