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Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania

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Abstract

Several studies have suggested that alterations in brain-derived neurotrophic factor (BDNF) and increased oxidative stress have a central role in bipolar disorder (BD). Intracerebroventricular (ICV) injection of ouabain (OUA) in rats alters oxidative stress parameters and decreases BDNF levels in the brain. In this context, the present study aims to investigate the effects of BDNF ICV administration on BDNF levels and oxidative stress parameters in brains of rats submitted to animal model of mania induced by OUA. Wistar rats received an ICV injection of OUA, artificial cerebrospinal fluid (ACSF), OUA plus BDNF, or ACSF plus BDNF. Locomotor activity and risk-taking behavior in the rats were measured using the open-field test. In addition, we analyzed the BDNF levels and oxidative stress parameters (TBARS, Carbonyl, CAT, SOD, GR, and GPx) in the frontal cortex and hippocampus of rats. The BDNF was unable to reverse the ouabain-induced hyperactivity and risk-taking behavior. Nevertheless, BDNF treatment increased BDNF levels, modulated the antioxidant enzymes, and protected the OUA-induced oxidative damage in the brain of rats. These results suggest that BDNF alteration observed in BD patients may be associated with oxidative damage, both seen in this disorder.

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Acknowledgments

We thank CNPq, FAPESC, CAPES, and UNESC for financial support.

Conflict of Interest

None of the authors or funding sources has conflict of interest.

Role of Funding Source

No external funding was used for this study.

Contributors

Samira S. Valvassori, João Quevedo, and Flavio Kapczinski designed the study, wrote the protocol and the first draft of the manuscript. Amanda V. Steckert, Camila O. Arent, and Josiane Budni made the biochemical analysis. Samira S. Valvassori and Luciano K. Jornada undertook the statistical analysis. Edemilson Mariot, Paula Tonin, and Samira S. Valvassori were responsible for the surgical procedures, pharmacological treatment, and behavioral tests. All authors contributed to and have approved the final manuscript.

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Authors and Affiliations

  1. Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Samira S. Valvassori, Camila O. Arent, Amanda V. Steckert, Roger B. Varela, Luciano K. Jornada, Paula T. Tonin, Josiane Budni, Edemilson Mariot & João Quevedo

  2. Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA

    Flávio Kapczinski & João Quevedo

  3. Laboratoryof Molecular Psychiatric and National Institute for Translational Medicine (INCT-TM), Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, 90035-003, Porto Alegre, RS, Brazil

    Flávio Kapczinski

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  1. Samira S. Valvassori
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  2. Camila O. Arent
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  3. Amanda V. Steckert
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Correspondence to Samira S. Valvassori or João Quevedo.

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Valvassori, S.S., Arent, C.O., Steckert, A.V. et al. Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania. Mol Neurobiol 52, 353–362 (2015). https://doi.org/10.1007/s12035-014-8873-8

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