Sex‐specific peripheral and central responses to stress‐induced depression and treatment in a mouse model
Open accessAbstract
Major depressive disorder affects ~20% of the world population and is characterized by strong sexual dimorphism with females being two to three times more likely to develop this disorder. Previously, we demonstrated that a combination therapy with dihydrocaffeic acid and malvidin‐glucoside to synergistically target peripheral inflammation and stress‐induced synaptic maladaptation in the brain was effective in alleviating chronic social defeat stress (CSDS)‐induced depression‐like phenotype in male mice. Here, we test the combination therapy in a female CSDS model for depression and compared sex‐specific responses to stress in the periphery and the central nervous system. Similar to male mice, the combination treatment is also effective in promoting resilience against the CSDS‐induced depression‐like behavior in female mice. However, there are sex‐specific differences in peripheral immune responses and differential gene regulation in the prefrontal cortex to chronic stress and to the treatment. These data indicate that while therapeutic approaches to combat stress‐related disorders may be effective in both sexes, the mechanisms underlying these effects differ, emphasizing the need for inclusion of both sexes in preclinical studies using animal models.
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Some rodents exposed to CVS or CSDS have higher blood levels of pro-inflammatory cytokines and chemokines than unstressed controls and stress-resilient mice.
“Similar to people with MDD, a subset of rodents exposed to CVS or CSDS also have higher levels of pro-inflammatory cytokines and chemokines, such as IL1A, IL1B, IL6, IL12, TNF, CCL2, and CCL5, in the bloodstream compared to unstressed control mice and stress-resilient mice”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [30]
The Results section (page not supplied) reports higher plasma levels of the listed cytokines and chemokines in female mice exposed to CSDS than in non-CSDS controls. It does not report findings for CVS or a direct comparison of those levels with stress-resilient mice; it reports correlations between some plasma markers and stress-related behavior instead. (LLM, conf=0.89)
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Parise, L. F., Cardona-Acosta, A. M., Parise, E. M., & Bolaños‐Guzmán, C. A. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780197640654.003.0030
Self-citationBurgos-Salcedo, J. D., & Cárdenas, C. S. (2025) · medRxiv · doi:10.1101/2025.09.14.25335729
- Authors
- Deonaraine, K. K., Wang, Q., Cheng, H., Chan, K. L., Lin, H., Liu, K., Parise, L. F., Cathomas, F., Leclair, K. B., Flanigan, M. E., Li, L., Aleyasin, H., Guevara, C., Hao, K., Zhang, B., Russo, S. J., & Wang, J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- James J. Peters VA Medical Center (US)
- Corresponding author
- Wang, Jun
- ORCID
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2020-09-11
- Volume
- 98
- Issue
- 12
- Pages
- 2541-2553
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- PMC
- PMC8561614
- OpenAlex
- W3084721587
- Cited by
- 21
- References
- 65
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Complementary and Integrative Health
- National Institute of Mental Health
- Office of Dietary Supplements
- U.S. Department of Veterans Affairs
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- sex differences, major depressive disorder, chronic social defeat stress, stress-induced depression, dihydrocaffeic acid, combination therapy, peripheral inflammation, depression resilience, female mice
- MeSH terms
- Social Defeat, Animals, Major Depressive Disorder, Disease Models, Animal, Female, Immunity, Male, Mice, Inbred C57BL, Mice, Transgenic, Sex Characteristics, Stress, Psychological, Prefrontal Cortex, Mice
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