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Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

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JIMD Reports - Case and Research Reports, Volume 13

Abstract

Maple syrup urine disease (MSUD) is an inborn metabolism error caused by a deficiency of branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to an accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their corresponding α-keto and α-hydroxy acids. Previous reports suggest that MSUD patients are at high risk for chronic neuropsychiatric problems. Therefore, in this study, we assessed variables that suggest depressive-like symptoms (anhedonia as measured by sucrose intake, immobility during the forced swimming test and body and adrenal gland weight) in rats submitted to chronic administration of BCAA during development. Furthermore, we determined if these parameters were sensitive to imipramine and N-acetylcysteine/deferoxamine (NAC/DFX). Our results demonstrated that animals subjected to chronic administration of branched-chain amino acids showed a decrease in sucrose intake without significant changes in body weight. We also observed an increase in adrenal gland weight and immobility time during the forced swimming test. However, treatment with imipramine and NAC/DFX reversed these changes in the behavioral tasks. In conclusion, this study demonstrates a link between MSUD and depression in rats. Moreover, this investigation reveals that the antidepressant action of NAC/DFX and imipramine might be associated with their capability to maintain pro-/anti-oxidative homeostasis.

Competing interests: None declared

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Acknowledgments

This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde – Universidade do Extremo Sul Catarinense (UNESC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Correspondence to Emilio L. Streck .

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Communicated by: Bruce A Barshop, MD, PhD

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Author Contribution

Giselli Scaini, Emilio L. Streck, and João Quevedo designed the study and wrote the protocol. Giselli Scaini, Gabriela C. Jeremias, Camila B. Furlanetto, and Diogo Dominguini conducted the experiments. Giselli Scaini and Clarissa M. Comim undertook the statistical analysis; and Giselli Scaini and Emilio L. Streck wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

Conflicts of Interest

Giselli Scaini, Gabriela C. Jeremias, Camila B. Furlanetto, Diogo Dominguini, Clarissa M. Comim, João Quevedo, Patrícia F. Schuck, Gustavo C. Ferreira, and Emilio L. Streck declare that they have no conflict of interest.

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All institutional and national guidelines for the care and use of laboratory animals were followed. All experimental procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Brazilian Society for Neuroscience and Behavior recommendations for animal care.

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Scaini, G. et al. (2013). Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_274

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