Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation

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.

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Funding

This work was supported by the deputy of research of Zanjan University of Medical Sciences (Grant No. A-12-769-16 &29).

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Conceived and designed the experiments and the study protocol: MJH & SEM; Performed the experiments: HM, SA, MM & SB; Analyzed the data: MJH, SA & HAK; Interpretation of the data: MJH & SEM; Wrote the paper: MJH, SA & SEM. Critical review of the manuscript: MJH, SA & SEM.

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Correspondence to Mir-Jamal Hosseini.

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Informed consent was obtained from all individual participants included in the study.

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All procedures were performed in line with the NIH Guide for the Care and Use of Laboratory Animals, which were approved by the Animal Ethics committee of Zanjan University of Medical Sciences (registration number: ZUMS.REC.1394.244).

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Mozafari, H., Amiri, S., Mehr, S.E. et al. Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation. Mol Biol Rep (2020). https://doi.org/10.1007/s11033-020-05696-w

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Keywords

  • Minocycline
  • Streptozotocin
  • Depression
  • Mitochondria
  • Neuroinflammation
  • Hippocampus