Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice

Amiri, S. and Haj-Mirzaiain, A. and Momeny, M. and Amini-Khoei, H. and Rahimi-Balaei, M. and Poursaman, S. and Rastegar, M. and Nikoui, V. and Mokhtari, T. and Ghazi-Khansari, M. and Hosseini, M.-J. (2017) Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice. Neuroscience, 340. pp. 373-383.

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Abstract

Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2 mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24 h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A2 (cPLA2) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: anxietyو depressionو innate immunityو mitochondriaو sterile inflammationو streptozotocin (STZ)
Subjects: QW Microbiology and Immunology
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Physiology
Depositing User: zahra bagheri .
Date Deposited: 21 Jun 2017 09:16
Last Modified: 28 Jun 2017 05:03
URI: http://eprints.skums.ac.ir/id/eprint/201

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