L-Arginine Exerts Excellent Anti-Stress Effects on Stress-Induced Shortened Lifespan, Cognitive Decline and Depression
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The anti-stress potential of dietary L-arginine (Arg) was assessed in psychosocially stress-loaded senescence-accelerated (SAMP10) mice. Although this strain of mouse is sensitive to stress, daily administration of Arg at 3 mg/kg significantly suppressed aging-related cognitive decline and behavioral depression at nine months of age and counteracted stress-induced shortened lifespan. To investigate the mechanism of the anti-stress effect of Arg in the brain, early changes in oxidative damage and gene expression levels were measured using SAMP10 mice that were stress-loaded for three days. Increased lipid peroxidation in the brains of stressed mice was significantly lowered by Arg intake. Several genes associated with oxidative stress response and neuronal excitotoxic cell death, including Nr4a1, Arc, and Cyr61, remarkably increased in response to psychosocial stress; however, their expression was significantly suppressed in mice that ingested Arg even under stress conditions. In contrast, the genes that maintain mitochondrial functions and neuronal survival, including Hba-a2 and Hbb-b2, were significantly increased in mice that ingested Arg. These results indicate that Arg reduces oxidative damage and enhances mitochondrial functions in the brain. We suggest that the daily intake of Arg plays important roles in reducing stress-induced brain damage and slowing aging.
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Animal studies suggest that stress and the resulting brain damage that can lead to depression are reduced with L-arginine.
“Although some animal studies have suggested that stress, and the resulting brain damage that can lead to depression will be reduced with L-arginine, there are few human studies in this regard [45].”
From Effect of l-arginine compared to placebo on sexual function in women with major depressive disorder: a randomized controlled trial (2024) · cites this paper as [45]
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- Authors
- Pervin, M., Unno, K., Konishi, T., & Nakamura, Y.
- Affiliations
- Shizuoka University (JP)
- Akita Prefectural University (JP)
- Corresponding author
- Pervin, Monira
- Unno, Keiko
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-01-06
- Volume
- 22
- Issue
- 2
- Pages
- 508
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7825557
- OpenAlex
- W3118741184
- Cited by
- 41
- References
- 62
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 5 · 2021: 1
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Kobayashi International Scholarship Foundation (6)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Keywords
- L-arginine, anti-stress effects, psychosocial stress, accelerated aging, cognitive decline, depression, lifespan reduction, oxidative stress, lipid peroxidation, mitochondrial function, Nur77, Arc, CYR61, excitotoxicity, dietary supplementation
- MeSH terms
- Animals, Arginine, Depression, Gene Expression Regulation, Hippocampus, Learning, Longevity, Male, Mice, Inbred C57BL, Stress, Physiological, Survival Analysis, Oxidative Stress, Gene Expression Profiling, Mice, Cysteine-Rich Protein 61, Nuclear Receptor Subfamily 4, Group A, Member 1, Cognitive Dysfunction
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