Oxytocin mitigated the depressive-like behaviors of maternal separation stress through modulating mitochondrial function and neuroinflammation
Abstract
Mother-infant contact has a critical role on brain development and behavior. Experiencing early-life adversities (such as maternal separation stress or MS in rodents) results in adaptations of neurotransmission systems, which may subsequently increase the risk of depression symptoms later in life. In this study, we show that Oxytocin (OT) exerted antioxidant and anti-inflammatory properties. Previous studies indicate that neuroinflammation and mitochondrial dysfunction are associated with the pathophysiology of depression. To investigate the antidepressant-like effects of OT, we applied MS paradigm (as a valid animal model of depression) to male mice at postnatal day (PND) 2 to PND 14 (3h daily, 9AM to 12AM) and investigated the depressive-like behaviors of these animals at PND 60 in different groups. Animals in this work were divided into 4 experimental groups: 1) saline-treated, 2) OT-treated, 3) atosiban (OT antagonist)-treated and, 4) OT+ atosiban-treated mice. We used forced swimming test (FST), splash test, sucrose preference test (SPT) and open field test (OFT) for behavioral assessment. Additionally, we used another set of animals to investigate the effects of MS and different treatments on mitochondrial function and the expression of the relevant genes for neuroinflammation. Our results showed that MS provoked depressive- like behaviors in the FST, SPT and splash test. In addition, our molecular findings revealed that MS is capable of inducing abnormal mitochondrial function and immune-inflammatory response in the hippocampus. Further, we observed that treating stressed animals with OT (intracerebroventricular, i.c.v. injection) attenuated the MS-induced depressive-like behaviors through improving mitochondrial function and decreasing the hippocampal expression of immune-inflammatory genes. In conclusion, we showed that MS-induced depressive-like behaviors in adult male mice are associated with abnormal mitochondrial function and immune-inflammatory responses in the hippocampus, and activation of OTergic system has protective effects against negative effects of MS on brain and behavior of animals.
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In cardiovascular comorbidity models, SAHA reduces oxidative stress and metabolic imbalance through downregulation of the NOX4/PGC-1α pathway.
“In cardiovascular comorbidity models, SAHA reduces oxidative stress and metabolic imbalance through downregulation of the NOX4/PGC-1α pathway (Kv et al., 2018; Amini-Khoei et al., 2017).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Amini-Khoei et al., 2017
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Is oxytocin “nature’s medicine”
Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394 · see citing works
Haj-Mirzaian, A., Amiri, S., Amini-Khoei, H., Hosseini, M.-J., Haj-Mirzaian, A., Momeny, M., Rahimi-Balaei, M., & Dehpour, A. R. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.023 · Cited by 100 · see citing works
Self-citationMitochondria, Oxytocin, and Vasopressin: Unfolding the Inflammatory Protein Response
Bordt, E. A., Smith, C. J., Demarest, T. G., Bilbo, S. D., & Kingsbury, M. A. (2019) · Neurotoxicity Research · doi:10.1007/s12640-018-9962-7 · Cited by 58 · see citing works
Ershadi, A. S. B., Amini-Khoei, H., Hosseini, M.-J., & Dehpour, A. R. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03263-8 · Cited by 25 · see citing works
Self-citationNasehi, L., Morassaei, B., Ghaffari, M., Sharafi, A., Dehpour, A. R., & Hosseini, M.-J. (2022) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2022-0098 · Cited by 5 · see citing works
Self-citationLv, 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
- Amini-Khoei, H., Mohammadi-Asl, A., Amiri, S., Hosseini, M.-J., Momeny, M., Hassanipour, M., Rastegar, M., Haj-Mirzaian, A., Mirzaian, A. H., Sanjarimoghaddam, H., Mehr, S. E., & Dehpour, A. R.
- Affiliations
- Shahrekord University of Medical Sciences (IR)
- University of Manitoba (CA)
- Zanjan University of Medical Sciences (IR)
- Shariati Hospital (IR)
- Rafsanjan University of Medical Sciences (IR)
- Tehran University of Medical Sciences (IR)
- Corresponding author
- Dehpour, Ahmad Reza
- ORCID
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 76
- Pages
- 169-178
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2594359131
- Cited by
- 153
- References
- 97
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 14 · 2023: 23 · 2022: 13 · 2021: 23 · 2020: 16 · 2019: 21 · 2018: 15 · 2017: 6
- FWCI
- 22.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences (94-04-30-31430)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, maternal separation stress, depression-like behavior, mitochondrial dysfunction, neuroinflammation, hippocampus, atosiban, childhood adversity, depression, antidepressant effects, mother-infant contact
- MeSH terms
- Animals, Behavior, Animal, Depression, Disease Models, Animal, Hippocampus, Hormone Antagonists, Inflammation, Male, Maternal Deprivation, Oxytocin, Vasotocin, Mitochondrial Diseases, Mice
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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