Atlas of exercise-induced brain activation in mice
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Atlas of exercise-induced brain activation in mice. / Skovbjerg, Grethe; Fritzen, Andreas Mæchel; Svendsen, Charlotte Sashi Aier; Perens, Johanna; Skytte, Jacob Lercke; Lund, Camilla; Lund, Jens; Madsen, Martin Rønn; Roostalu, Urmas; Hecksher-Sørensen, Jacob; Clemmensen, Christoffer.
In: Molecular Metabolism, Vol. 82, 101907, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Atlas of exercise-induced brain activation in mice
AU - Skovbjerg, Grethe
AU - Fritzen, Andreas Mæchel
AU - Svendsen, Charlotte Sashi Aier
AU - Perens, Johanna
AU - Skytte, Jacob Lercke
AU - Lund, Camilla
AU - Lund, Jens
AU - Madsen, Martin Rønn
AU - Roostalu, Urmas
AU - Hecksher-Sørensen, Jacob
AU - Clemmensen, Christoffer
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Brain activity
KW - c-Fos
KW - Exercise
KW - Stress
KW - Treadmill running
KW - Wheel running
U2 - 10.1016/j.molmet.2024.101907
DO - 10.1016/j.molmet.2024.101907
M3 - Journal article
C2 - 38428817
AN - SCOPUS:85187230215
VL - 82
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
M1 - 101907
ER -
ID: 385707036