Physical exercise mitigates the cognitive impairments by promoting ER-phagy in mice model of Alzheimer's disease.

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2025-05-23 DOI:10.1016/j.bbr.2025.115650

Lili Li, Shiyin Li, Lei Cai, Xiaofeng Yang, Yifeng Feng, Liying Zhang, Xiaofei He, Mingyue Li

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引用次数: 0

Abstract

Alzheimer's disease (AD) is the primary cause of dementia in older individuals, exhibiting an increasing incidence worldwide. Endoplasmic reticulum (ER) quality control has been receiving attention in the pathology of AD. The accumulation of misfolded proteins in the ER will activates the unfolded protein response (UPR), leading to cellular apoptosis. Using a mouse model of 5xFAD, we found that physical exercise (PE) promoted the clearance of ER fragments and inhibited the ER stress via ER autophagy (ER - Phagy). As a result, physical exercise reduced Aβ deposition, inhibited the neuronal apoptosis, ameliorated the emotional and cognitive impairments. Mechanistically, these PE related effects may be linked to the increased FAM134B, an ER-Phagy receptor, by up-regulating neuronal progranulin (Pgrn). Recombinant Pgrn injection could mimic the protective effects of PE, whereas down-regulation of Pgrn could abolish the PE-associated protection. Our findings indicate that physical exercise, as a readily accessible lifestyle intervention, holds significant potential for preventing diseases related to the global aging population.

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体育锻炼通过促进er吞噬减轻阿尔茨海默病小鼠模型的认知障碍。

阿尔茨海默病（AD）是老年人痴呆症的主要原因，在世界范围内发病率不断上升。内质网质量控制在阿尔茨海默病的病理研究中一直受到重视。错误折叠蛋白在内质网中的积累会激活未折叠蛋白反应（UPR），导致细胞凋亡。通过小鼠5xFAD模型，我们发现体育锻炼（PE）通过内质网自噬（ER - Phagy）促进内质网片段的清除，抑制内质网应激。结果表明，体育锻炼可减少a β沉积，抑制神经元凋亡，改善情绪和认知障碍。从机制上讲，这些PE相关效应可能与通过上调神经元颗粒前蛋白（Pgrn）而增加的er吞噬受体FAM134B有关。注射重组Pgrn可模拟PE的保护作用，而下调Pgrn可消除PE相关的保护作用。我们的研究结果表明，体育锻炼作为一种容易获得的生活方式干预，在预防与全球老龄化人口相关的疾病方面具有巨大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.