运动诱导的小鼠大脑激活图谱。

Atlas of exercise-induced brain activation in mice.

机构信息

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Gubra, Hørsholm, Denmark.

August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Mol Metab. 2024 Apr;82:101907. doi: 10.1016/j.molmet.2024.101907. Epub 2024 Feb 28.

DOI:10.1016/j.molmet.2024.101907

PMID:38428817

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10943479/

Abstract

OBJECTIVES

There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative diseases. In this study, we utilize forced treadmill running and distance-matched voluntary wheel running, coupled with light sheet 3D brain imaging and c-Fos immunohistochemistry, to generate a comprehensive atlas of exercise-induced brain activation in mice.

METHODS

To investigate the effects of exercise on brain activity, we compared whole-brain activation profiles of mice subjected to treadmill running with mice subjected to distance-matched wheel running. Male mice were assigned to one of four groups: a) an acute bout of voluntary wheel running, b) confinement to a cage with a locked running wheel, c) forced treadmill running, or d) placement on an inactive treadmill. Immediately following each exercise or control intervention, blood samples were collected for plasma analysis, and brains were collected for whole-brain c-Fos quantification.

RESULTS

Our dataset reveals 255 brain regions activated by acute exercise in mice, the majority of which have not previously been linked to exercise. We find a broad response of 140 regulated brain regions that are shared between voluntary wheel running and treadmill running, while 32 brain regions are uniquely regulated by wheel running and 83 brain regions uniquely regulated by treadmill running. In contrast to voluntary wheel running, forced treadmill running triggers activity in brain regions associated with stress, fear, and pain.

CONCLUSIONS

Our findings demonstrate a significant overlap in neuronal activation signatures between voluntary wheel running and distance-matched forced treadmill running. However, our analysis also reveals notable differences and subtle nuances between these two widely used paradigms. The comprehensive dataset is accessible online at www.neuropedia.dk, with the aim of enabling future research directed towards unraveling the neurobiological response to exercise.

摘要

目的

人们对揭示运动增强认知、记忆和情绪、降低神经退行性疾病风险的机制非常感兴趣。在这项研究中，我们利用强制跑步机跑步和距离匹配的自愿轮跑，结合光片 3D 脑成像和 c-Fos 免疫组织化学，生成了小鼠运动诱导脑激活的综合图谱。

方法

为了研究运动对大脑活动的影响，我们比较了接受跑步机跑步的小鼠和接受距离匹配的轮跑的小鼠的全脑激活图谱。雄性小鼠被分配到以下四个组之一：a）急性自愿轮跑，b）限制在带锁定轮的笼子里，c）强制跑步机跑，或 d）放置在不活动的跑步机上。在每次运动或对照干预后，立即采集血液样本进行血浆分析，并采集大脑样本进行全脑 c-Fos 定量。

结果

我们的数据集揭示了 255 个在小鼠急性运动中被激活的大脑区域，其中大多数以前与运动无关。我们发现 140 个受调节的大脑区域广泛响应，这些区域在自愿轮跑和跑步机跑之间共享，而 32 个大脑区域仅由轮跑调节，83 个大脑区域仅由跑步机跑调节。与自愿轮跑不同，强制跑步机跑会引发与应激、恐惧和疼痛相关的大脑区域的活动。