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Physical activity and muscle-brain crosstalk
Pedersen BK.. Nature reviews. Endocrinology, 2019-07-01
Topic: Risk, prevention and care in population studies
Neurological and mental illnesses account for a considerable proportion of the global burden of disease. Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and it has a role in restoring and maintaining cognitive function and metabolic control. The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function. Muscle secretes myokines that contribute to the regulation of hippocampal function. Evidence is accumulating that the myokine cathepsin B passes through the blood-brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning. Exercise increases neuronal gene expression of FNDC5 (which encodes the PGC1α-dependent myokine FNDC5), which can likewise contribute to increased brain-derived neurotrophic factor levels. Serum levels of the prototype myokine, IL-6, increase with exercise and might contribute to the suppression of central mechanisms of feeding. Exercise also increases the PGC1α-dependent muscular expression of kynurenine aminotransferase enzymes, which induces a beneficial shift in the balance between the neurotoxic kynurenine and the neuroprotective kynurenic acid, thereby reducing depression-like symptoms. Myokine signalling, other muscular factors and exercise-induced hepatokines and adipokines are implicated in mediating the exercise-induced beneficial impact on neurogenesis, cognitive function, appetite and metabolism, thus supporting the existence of a muscle-brain endocrine loop.
Key findings
- The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function.
Why it matters
This review argues that exercise affects the brain partly through substances released by working muscle ("myokines"). It describes evidence that one, cathepsin B, "passes through the blood-brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning", while describing that evidence as still "accumulating". It links exercise to "decreased risks of dementia" as an association, but it is a review that tests no treatment and does not examine Alzheimer's disease in patients.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Endocrinology) |
| Journal's citation record | 3 / 4 | Nature Reviews Endocrinology: journal h-index 265 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 760 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 84.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 17.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 4 / 4 | Cited 352 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bente Klarlund Pedersen: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Copenhagen: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30837717) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Pedersen, B. K. (2019). Physical activity and muscle-brain crosstalk. Nature reviews. Endocrinology. https://doi.org/10.1038/s41574-019-0174-x
Vancouver
Pedersen BK. Physical activity and muscle-brain crosstalk. Nature reviews. Endocrinology. 2019. doi:10.1038/s41574-019-0174-x. PMID: 30837717.
BibTeX
@article{pedersen2019-30837717,
author = {Pedersen, B. K.},
title = {{Physical activity and muscle-brain crosstalk}},
journal = {Nature reviews. Endocrinology},
year = {2019},
doi = {10.1038/s41574-019-0174-x},
pmid = {30837717},
url = {https://doi.org/10.1038/s41574-019-0174-x}
}
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