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Molecular Neurobiology

, Volume 56, Issue 4, pp 2379–2393 | Cite as

Inhibition of GSK-3β on Behavioral Changes and Oxidative Stress in an Animal Model of Mania

  • Gustavo C. Dal-PontEmail author
  • Wilson R. Resende
  • Roger B. Varela
  • Samira Menegas
  • Kerolen S. Trajano
  • Bruna R. Peterle
  • João Quevedo
  • Samira S. Valvassori
Article

Abstract

The present study evaluated the effects of AR-A014418 on behavioral and oxidative stress parameters of rats submitted to the animal model of mania induced by ouabain (OUA). Wistar rats were submitted to stereotaxic surgery and received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid (aCSF), OUA, or AR-A014418. After 7 days, the animals were submitted to open-field test. After behavioral analysis, the brains were dissected in frontal cortex and hippocampus to the evaluation of oxidative stress. The OUA induced manic-like behavior in rats, which was reversed by AR-A014418 treatment. The ICV administration of OUA increases the levels of superoxide in submitochondrial particles, lipid hydroperoxide (LPH), 4-hydroxynonenal (4-HNE), 8-isoprostane, protein carbonyl, 3-nitrotyrosine, and activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in both structures evaluated. In general, the treatment with AR-A014418 reversed these effects of OUA on the submitochondrial particles, LPH, 4-HNE, 8-isoprostane, protein carbonyl, 3-nitrotyrosine levels, and SOD activity. Furthermore, the injection of OUA decreased the catalase activity, and AR-A014418 promoted an increase in activity of this enzyme in the brain structures. These results suggest that GSK-3β inhibition can modulate manic-like behaviors. Also, it can be suggested that inhibition of GSK-3β can be effective against oxidative stress. However, more studies are needed to better elucidate these mechanisms.

Graphical Abstract

The effects of AR-A014418 on the behavioral and oxidative stress parameters in the animal model of mania induced by ouabain. Superoxide = superoxide production in submitochondrial particles; LPH = lipid hydroperoxide; 4-HNE = 4-hydroxynonenal; SOD = superoxide dismutase; GPx = glutathione peroxidase; GR = glutathione reductase.

Keywords

Bipolar disorder Ouabain Na+K+ATPase GSK-3β AR-A014418 Oxidative stress 

Notes

Acknowledgements

This research was supported by grants from CAPES, CNPq, FAPESC, Instituto Cérebro e Mente, and UNESC. SSV and JQ are CNPq Research Fellows. GCDP and SM are holders of a FAPESC studentship and RBV is a holder of a CAPES studentship.

Compliance with Ethical Standards

Conflict Interest

This research has no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gustavo C. Dal-Pont
    • 1
    Email author
  • Wilson R. Resende
    • 1
  • Roger B. Varela
    • 1
  • Samira Menegas
    • 1
  • Kerolen S. Trajano
    • 1
  • Bruna R. Peterle
    • 1
  • João Quevedo
    • 1
    • 2
    • 3
    • 4
  • Samira S. Valvassori
    • 1
  1. 1.Translational Psychiatry Laboratory, Graduate Program in Health SciencesUniversity of Southern Santa Catarina (UNESC)CriciúmaBrazil
  2. 2.Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolThe University of Texas Health Science Center at Houston (UTHealth)HoustonUSA
  3. 3.Neuroscience Graduate ProgramThe University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonUSA
  4. 4.Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolThe University of Texas Health Science Center at Houston (UTHealth)HoustonUSA

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