Neurological mechanism-based analysis of the role and characteristics of physical activity in the improvement of depressive symptoms
Abstract
Depression is a common mental disorder characterized by a high prevalence and significant adverse effects, making the searching for effective interventions an urgent priority. In recent years, physical activity (PA) has increasingly been recognized as a standard adjunctive treatment for mental disorders owing to its low cost, easy application, and high efficiency. Epidemiological data shows positive preventive and therapeutic effects of PA on mental illnesses such as depression. This article systematically describes the prophylactic and therapeutic effects of PA on depression and its biological basis. A comprehensive literature analysis reveals that PA significantly improves depressive symptoms by upregulating the expression of "exerkines" such as irisin, adiponectin, and BDNF to positively impacting neuropsychiatric conditions. In particular, lactate could also play a critical role in the ameliorating effects of PA on depression due to the findings about protein lactylation as a novel protein post-transcriptional modification. The literature also suggests that in terms of brain structure, PA may improve hippocampal volume, basal ganglia (neostriatum, caudate-crustal nucleus) and PFC density in patients with MDD. In summary, this study elucidates the multifaceted positive effects of PA on depression and its potential biological mechanisms with a particular emphasis on the roles of various exerkines. Future research may further investigate the effects of different types, intensities, and durations of PA on depression, as well as how to better integrate PA interventions into existing treatment strategies to achieve optimal outcomes in mental health interventions.
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Increased intracellular lactate elevates histone lactylation, suggesting that Kla acts as a metabolically sensitive epigenetic signal.
“Increased intracellular lactate, such as during mitochondrial respiratory inhibition, elevates histone lactylation, suggesting that Kla acts as a metabolically sensitive epigenetic signal (Wang et al., 2025).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Wang et al., 2025
ATAC-seq detects chromatin accessibility changes associated with stress or disease states.
“ChIP-seq reveals genome-wide distributions of histone modifications and regulatory elements (Nakato and Sakata, 2021), whereas ATAC-seq detects chromatin accessibility changes associated with stress or disease states (Wang et al., 2025).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Wang et al., 2025
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Cited by
Sorted by citations
Lv, L.-Z., Wang, Z.-D., Ren, J.-J., Li, L.-H., Liu, X.-B., Li, J.-L., Zhu, H., Jiang, B., Han, Y.-P., Zhou, X.-M., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1722453 · Cited by 7 · see citing works
- Authors
- Wang, N., Zhu, S., Chen, S., Zou, J., Zeng, P., & Tan, S.
- Affiliations
- University of South China (CN)
- China Academy of Chinese Medical Sciences (CN)
- Corresponding author
- Tan, Sijie
- Venue
- Reviews in the Neurosciences
- Publisher
- Walter de Gruyter GmbH
- Published
- 2025-01-21
- Volume
- 36
- Issue
- 5
- Pages
- 455-478
- ISSN
- 0334-1763 (ISSN-L)
- 2191-0200
- OpenAlex
- W4406627671
- Cited by
- 12
- References
- 296
- Citations by year
- 2026: 8 · 2025: 4
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reviews in the Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hunan Provincial Natural Science Foundation (2023JJ30504)
- Jiangxi Provincial Natural Science Foundation (20242BAB25472)
- Hunan Education Department (22A0311)
- The Science and Technology Innovation Project for College Students of Hunan Province (S202310555219 (Zhang Yun,), 461 (Xu Heng))
- Hubei Key Laboratory for Kidney Disease Pathogenesis (2023SB101)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- physical activity, depression, major depressive disorder, exerkines, irisin, adiponectin, brain-derived neurotrophic factor, lactate, lactylation, hippocampal volume, basal ganglia, prefrontal cortex, neuroplasticity, adjunctive therapy
- MeSH terms
- Animals, Brain, Depression, Exercise Therapy, Humans, Exercise
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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