Exercise alleviates cognitive decline of natural aging rats by upregulating Notch-mediated autophagy signaling.

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2024-12-10 DOI:10.1016/j.brainres.2024.149398

Dandan Chen, Yuan Guo, Meng Zhang, Xingran Liu, Baowen Zhang, Xianjuan Kou

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Abstract

Notch signaling, a classical signaling pathway of neurogenesis, is downregulated during the aging and age-related neurodegenerative diseases. Exercise has been proposed as an effective lifestyle intervention for delaying cognitive decline. However, it remains unclear whether exercise intervention could alleviate cognitive decline by modulating neurogenesis in naturally aging rats. In this study, 21-month-old natural aging rats were used to study brain aging. The natural aging rats underwent different forms of exercise training (aerobic exercise or strength training or comprehensive exercise with aerobic exercise and strength training) for 12 consecutive weeks. The cognitive function of natural aging rats was determined by Morris Water Maze. Notch signaling, autophagy-related proteins and hippocampal neurogenesis were examined by immunofluorescence, qRT-PCR and Western blot. Results showed that natural aging rats exhibited cognitive decline, accumulation of AD pathological proteins (APP and Aβ), and decreased neurogenesis (decreased DCX, Ki67 and GFAP), compared with the young control rats. Moreover, a significant decline in Notch signaling and autophagy was found in the hippocampus of natural aging rats. However, different forms of exercise upregulated Notch signaling and its downstream target genes, as well as autophagy-related proteins, including LC3, Beclin1, and p62. In summary, our data suggest that different forms of exercise can mitigate brain aging by upregulating Notch signaling and autophagy, thereby increasing hippocampal neurogenesis and improves spatial learning and memory abilities.

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运动通过上调notch介导的自噬信号通路，减轻自然衰老大鼠的认知能力下降。

Notch 信号是神经发生的经典信号通路，在衰老和与年龄相关的神经退行性疾病中被下调。运动被认为是延缓认知功能衰退的一种有效生活方式。然而，运动干预能否通过调节自然衰老大鼠的神经发生来缓解认知功能衰退，目前仍不清楚。本研究使用 21 个月大的自然衰老大鼠来研究脑衰老。自然衰老大鼠接受了连续 12 周的不同形式的运动训练（有氧运动或力量训练或有氧运动和力量训练的综合运动）。通过莫里斯水迷宫测定自然衰老大鼠的认知功能。通过免疫荧光、qRT-PCR和Western blot检测了Notch信号转导、自噬相关蛋白和海马神经发生。结果显示，与年轻对照组相比，自然衰老大鼠表现出认知能力下降、AD病理蛋白（APP和Aβ）积累和神经发生减少（DCX、Ki67和GFAP减少）。此外，在自然衰老大鼠的海马中还发现了Notch信号转导和自噬的明显下降。然而，不同形式的运动会上调 Notch 信号转导及其下游靶基因，以及自噬相关蛋白，包括 LC3、Beclin1 和 p62。总之，我们的数据表明，不同形式的运动可以通过上调Notch信号和自噬来缓解大脑衰老，从而增加海马神经发生，提高空间学习和记忆能力。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.