Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozot
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ORIGINAL ARTICLE
Minocycline attenuates depressive‑like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation Haniyeh Mozafari1,2 · Shayan Amiri3,4 · Shahram Ejtemaei Mehr4 · Majid Momeny5 · Hossein Amini‑khoei6 · Soroush Bijani1,2 · Mir‑Jamal Hosseini1,2 Received: 28 March 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract Neuroinflammation and mitochondrial dysfunction are suggested as mechanisms which are implicated in the pathophysiology of depression. Streptozotocin (STZ) is known to produce immune-inflammatory responses and mitochondrial dysfunction in different types of animal models of disease (e.g. type-1 diabetes and Alzheimer’s disease). Therefore, a single low dose of Streptozotocin (STZ; intracerebroventricular, i.c.v, 0.2 mg/mouse) was used to induce an animal model of depression. The present study aims to investigate the effects of short (24 h) and long (14 days) exposure to minocycline on STZ-induced depressive-like behaviors (n = 6–8), hippocampal oxidative state biomarkers (n = 4), and the expression of hippocampal genes related to innate immunity (n = 3) in the hippocampus of male adult mice. In addition, the protective effects of different modes of minocycline (acute pretreatment (20 mg/kg, 1 h before STZ), acute post-treatment (20 mg/kg, 24 h after STZ), chronic pretreatment (5 mg/kg/day for 14 days before STZ), and chronic post-treatment (5 mg/kg/day for 14 days after STZ) were compared with the STZ effects. As the data showed, both short and long effects of STZ were associated with the depressive-like behaviors, abnormal mitochondrial function, and upregulation of neuroinflammatory genes in the hippocampus. Different modes of minocycline treatment could attenuate the negative impact of STZ on animals. The data suggested that minocycline at a human therapeutic dose (5 mg/kg) had protective effects against acute cellular damage induced by oxidation and the consequent inflammatory responses. Keywords Minocycline · Streptozotocin · Depression · Mitochondria · Neuroinflammation · Hippocampus
Introduction
Haniyeh Mozafari and Shayan Amiri have contributed equally to this work. * Mir‑Jamal Hosseini [email protected] 1
Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
2
Departments of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, P. O. Box: 45139‑56184, Iran
3
Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Depression, a debilitating psychiatric disorder accompanied with some diseases such as cardiovascular disorders (CVD), is considered as one of most challenging health issues in the current century [1]. In recent decades, extensive attempts have been made to understand the underpinning 4
Department of Pharmacology, School of Medicine, Tehran University of Medical S
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