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Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex

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Abstract

Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.

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Acknowledgments

We thank the authors who have provided relevant clarification on their articles. The Laboratory of Bioenergetics and Laboratory of Neurosciences (Brazil) are some of the centres of the National Institute for Molecular Medicine (INCT-MM) and members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). The Center for Translational Psychiatry (USA) is funded by the Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston. This research was supported by grants from CNPq (ELS and JQ), FAPESC (ELS and JQ), Instituto Cérebro e Mente (JQ) and UNESC (ELS and JQ).

Authors’ contributions

KC, LMG and MC participated in the study conception and design, biochemical analysis and drafting of the article and approved the version to be published. LJT, JR and ITM performed the biochemical analysis and approved the version to be published. COA and EM performed the behaviour analysis and approved the version to be published. LWK and MRB performed the gene expression analysis and approved the version to be published. GS, ELS and JQ started the project, participated in study conception and design, interpreted the data, drafted the article and approved the version to be published.

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Authors and Affiliations

  1. Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil

    Kizzy Cancelier, Lara M. Gomes, Milena Carvalho-Silva, Letícia J. Teixeira, Joyce Rebelo, Isabella T. Mota, Giselli Scaini & Emilio L. Streck

  2. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center (UTHealth), 1941 East Road, Ste. 5102, Houston, TX, USA

    João Quevedo & Giselli Scaini

  3. Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center (UTHealth), Houston, TX, USA

    João Quevedo

  4. Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil

    Camila O. Arent, Edemilson Mariot & João Quevedo

  5. Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Luiza W. Kist & Maurício R. Bogo

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  1. Kizzy Cancelier
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  2. Lara M. Gomes
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  3. Milena Carvalho-Silva
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Correspondence to Giselli Scaini.

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Cancelier, K., Gomes, L.M., Carvalho-Silva, M. et al. Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex. Mol Neurobiol 54, 3935–3947 (2017). https://doi.org/10.1007/s12035-016-9933-z

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