Atlas of exercise-induced brain activation in mice

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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, with the aim of enabling future research directed towards unraveling the neurobiological response to exercise.

TidsskriftMolecular Metabolism
Antal sider14
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We thank Thomas Topilko and Anders Bue Klein for helpful scientific discussions. G.S. receives funding from the Innovation Fund (grant number 9065-00237 B). C.C. receives funding from the Novo Nordisk Foundation Center for Basic Metabolic Research, an independent Research Center partially funded by an unconditionally donation from the Novo Nordisk Foundation (grant number NNF18CC0034900). A.M.F. is funded by the Novo Nordisk Foundation (grant number NNF 220C0074110). Figure 1 A was created using .

Publisher Copyright:
© 2024 The Author(s)

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