Administration of branched-chain amino acids alters epigenetic regulatory enzymes in an animal model of Maple Syrup Urin
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ORIGINAL ARTICLE
Administration of branched-chain amino acids alters epigenetic regulatory enzymes in an animal model of Maple Syrup Urine Disease Emilio L. Streck 1 & Felipe P. Bussular 1 & Leticia B. Wessler 1 & Mariane B. Duarte 1 & Victoria L. Rezende 1 & Matheus S. Rodrigues 2 & Carolina A. Torres 1 & Isabela S. Lemos 1 & Gabriela Candiotto 1 & Fernanda F. Gava 2 & Jade de Oliveira 3 & Samira S. Valvassori 2 Received: 23 July 2020 / Accepted: 11 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder that affects the activity of the branched-chainα-keto acid dehydrogenase complex (BCDK). This deficiency on BCDK complex results in the accumulation of branched-chain amino acids (BCAA) leucine, isoleucine, valine, and their corresponding α-keto acids. Epigenetic changes can negatively affect the metabolism of BCAA. These changes are catalyzed by the epigenetic regulatory enzymes, e.g., DNA methyltransferase (DNMT), histone deacetylases (HDAC), and histone acetyltransferases (HAT). However, the impacts of BCAA administration on the activity of epigenetic regulatory enzymes in the brain of MSUD patients are still unknown. In this study, we aimed to demonstrate the impact of BCAA administration on the activity of DNMT, HDAC, and HAT in the brain structures of infant rats, an animal model of MSUD. For that, we administered a BCAA pool to infant rats for 21 days. We demonstrated that BCAA administration significantly increased the DNMT and HDAC activities in the hippocampus and striatum, but not in the cerebral cortex of MSUD infant rats. A positive correlation was observed between HDAC and DNMT activities in the hippocampus and striatum of animals exposed to BCAA injections. Our results showed that the BCAA administration could modulate epigenetic regulatory enzymes, mainly DNMT and HDAC, in the brains of infant rats. Therefore, we suggest that the increase in the activity of DNMT and HDAC in the hippocampus and striatum could partially explain the neurological impairments presented in animal models of MSUD. Keywords Maple Syrup Urine Disease . Branched-chain amino acids . Epigenetics . DNA methyltransferase . Histone deacetylases . Histone acetyltransferases
Introduction Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder caused by a deficiency in the branched* Emilio L. Streck [email protected] 1
Laboratório de Doenças Neurometabólicas, Laboratório de Neurologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, SC Criciúma 88806-000, Brazil
2
Laboratório de Psiquiatria Translacional, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC 88806-000, Brazil
3
Programa de Pós-graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul Porto Alegre 90035-000,
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