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Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation

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Abstract

There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II–III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II–III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.

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Acknowledgments

Laboratório de Bioenergética and Laboratório de Neurociências (Brazil) are centers of the National Institute for Translational Medicine (INCT-TM) as well as members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq (ELS, JQ, MLA and FK), FAPESC (JQ and ELS), Instituto Cérebro e Mente (JQ and ELS) and UNESC (JQ and EST). ELS, FK, MLA, GTR and JQ are CNPq Research Fellows. CLG, GZR WRR and GZR are holders of a CAPES studentship, GS and SSV is holder of a CNPq studentship, and GKF is holder of a FAPESC studentship.

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Authors and Affiliations

  1. Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil

    Emilio L. Streck, Giselli Scaini, Gabriela C. Jeremias, Gislaine T. Rezin, Cinara L. Gonçalves & Gabriela K. Ferreira

  2. Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Gislaine Z. Réus, Wilson R. Resende, Samira S. Valvassori & João Quevedo

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

    Gislaine Z. Réus, Flávio Kapczinski & João Quevedo

  4. Bipolar Disorders Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Flávio Kapczinski

  5. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    Mônica L. Andersen

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  1. Emilio L. Streck
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  2. Giselli Scaini
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  3. Gabriela C. Jeremias
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  4. Gislaine T. Rezin
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  6. Gabriela K. Ferreira
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  9. Samira S. Valvassori
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  10. Flávio Kapczinski
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Correspondence to Emilio L. Streck.

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Streck, E.L., Scaini, G., Jeremias, G.C. et al. Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation. Neurochem Res 40, 1144–1152 (2015). https://doi.org/10.1007/s11064-015-1575-4

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