Oxytocin mitigated the depressive-like behaviors of maternal separation stress through modulating mitochondrial function and neuroinflammation

Amini-Khoei, H. and Mohammadi-Asl, A. and Amiri, S. and Hosseini, M.-J. and Momeny, M. and Hassanipour, M. and Rastegar, M. and Haj-Mirzaian, A. and Mirzaian, A.H. and Sanjarimoghaddam, H. and Mehr, S.E. and Dehpour, A.R. (2017) Oxytocin mitigated the depressive-like behaviors of maternal separation stress through modulating mitochondrial function and neuroinflammation. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 76. pp. 169-178.

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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.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: Depression, Maternal separation stress, Mitochondrial function, Neuroinflammation, Oxytocin
Subjects: WM Psychiatry
QV pharmacology > QV 752 Pharmacognosy
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Physiology
Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: zahra bagheri .
Date Deposited: 19 Jun 2017 04:35
Last Modified: 19 Jun 2017 08:23
URI: http://eprints.skums.ac.ir/id/eprint/137

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