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Oxytocin Mitigated the Depressive-Like Behaviors of Maternal Separation Stress Through Modulating Mitochondrial Function and Neuroinflammation Publisher Pubmed



Aminikhoei H1, 2 ; Mohammadiasl A3, 4 ; Amiri S3, 5 ; Hosseini MJ6, 7 ; Momeny M8 ; Hassanipour M9, 10 ; Rastegar M5 ; Hajmirzaian A3, 4 ; Mirzaian AH3, 4 ; Sanjarimoghaddam H3 ; Mehr SE3, 4 ; Dehpour AR3, 4
Authors
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Authors Affiliations
  1. 1. Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
  2. 2. Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
  6. 6. Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran
  7. 7. Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
  8. 8. Hematology/Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Kerman, Iran
  10. 10. Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Source: Progress in Neuro-Psychopharmacology and Biological Psychiatry Published:2017


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 (3 h daily, 9 AM to 12 AM) 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. © 2017 Elsevier Inc.
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