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Basic Science and Pathogenesis
1Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
Summary
Exercise may not boost brain-targeting exerkines in the brain, challenging their role in neuroprotection. This study examined exerkine expression across multiple organs after treadmill training in rats.
Area of Science:
- Neuroscience
- Exercise Physiology
- Molecular Biology
Background:
- Exercise provides neuroprotection and cognitive benefits against Alzheimer's disease.
- These benefits are hypothesized to stem from brain-targeting exerkines.
- The multi-organ responsiveness of these exerkines is not well understood.
Purpose of the Study:
- To investigate the expression and responsiveness of brain-targeting exerkines across various organs following exercise.
- To determine if exercise alters brain-targeting exerkine levels in the brain.
Main Methods:
- Utilized the MoTrPact dataset, analyzing multi-omics data from rats undergoing treadmill training.
- Collected blood and 18 solid tissues, including brain regions (cortex, hippocampus, hypothalamus).
- Examined protein and transcriptional expression of key brain-targeting exerkines.
Main Results:
- Exerkine responsiveness varied by tissue, with prosaposin showing the highest.
- Brain-targeting exerkine expression in the brain remained unchanged in both sexes throughout the 8-week training.
- Protein and transcriptional levels of studied exerkines were not significantly altered in the brain.
Conclusions:
- Brain-targeting exerkines did not change in the brain post-exercise, contrary to prior assumptions.
- This challenges the existence or function of a body-brain exerkine axis in exercise-induced neuroprotection.
- The role of these exerkines in mediating exercise's cognitive benefits warrants further investigation.
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