PGC-1α–FNDC5–BDNF signaling pathway in skeletal muscle confers resilience to stress in mice subjected to chronic social defeat
Abstract
Skeletal muscle consumes two thirds of the body's energy and may play a role in stress-related disorders. Evidence suggests that the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α)-fibronectin type III domain-containing 5 (FNDC5)-brain-derived neurotrophic factor (BDNF) signaling pathway in skeletal muscle plays a key role in conferring the beneficial effects of exercise. In this study, we aimed to determine whether this pathway contributes to the resilience or susceptibility of mice subjected to chronic social defeat stress (CSDS). BDNF-tropomyosin receptor kinase B (TrkB) and proBDNF-p75 NTR signaling in the medial prefrontal cortex and nucleus accumbens of susceptible but not resilient mice were significantly altered compared with the controls. Furthermore, the levels of PGC-1α, FNDC5, and BDNF, as well as the p-TrkB/TrkB ratio in the skeletal muscle of susceptible but not resilient mice, were significantly lower than those of the controls, but the levels of proBDNF and p75 NTR in the skeletal muscle of susceptible mice were significantly higher than those of the controls. Moreover, there were significant positive associations between social interaction test data and the expression of PGC-1α, FNDC5, and BDNF or the p-TrkB/TrkB ratio in skeletal muscle. These results suggest that the downregulation of the PGC-1α-FNDC5-BDNF signaling pathway in skeletal muscle contributes to resilience vs. susceptibility to CSDS. Therefore, alterations in this pathway in skeletal muscle may play a crucial role in mediating stress-related disorders.
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Social defeat increases NAc PGC1α and its downstream myokine FNDC5.
“Social defeat increases NAc PGC1α and its downstream myokine FNDC5, and FNDC5 is upregulated more in resilient mice [130].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [130]
FNDC5 is upregulated more in resilient mice.
“Social defeat increases NAc PGC1α and its downstream myokine FNDC5, and FNDC5 is upregulated more in resilient mice [130].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [130]
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The molecular and cellular mechanisms of depression: a focus on reward circuitry
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- Authors
- Zhan, G., Huang, N., Li, S., Hua, D., Zhang, J., Fang, X., Yang, N., Luo, A., & Yang, C.
- Affiliations
- Tongji Hospital (CN)
- Corresponding author
- Luo, Ailin
- Yang, Chun
- Venue
- Psychopharmacology
- Published
- 2018-09-26
- Volume
- 235
- Issue
- 11
- Pages
- 3351-3358
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2893805293
- Cited by
- 32
- References
- 45
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 7 · 2017: 2
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81703482, 81500931, 81571047, 81771159)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- PGC-1α, FNDC5, brain-derived neurotrophic factor, chronic social defeat stress, skeletal muscle, stress resilience, TrkB, proBDNF, medial prefrontal cortex, nucleus accumbens, social interaction, stress-related disorders
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Chronic Disease, Fibronectins, Interpersonal Relations, Male, Mice, Inbred C57BL, Nucleus Accumbens, Physical Conditioning, Animal, Stress, Psychological, Signal Transduction, Down-Regulation, Muscle, Skeletal, Brain-Derived Neurotrophic Factor, Mice, Resilience, Psychological
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