Administration of branched-chain amino acids alters epigenetic regulatory enzymes in an animal model of Maple Syrup Urine Disease

被引：5

作者：

Streck, Emilio L. ^{[1
]}

Bussular, Felipe P. ^{[1
]}

Wessler, Leticia B. ^{[1
]}

Duarte, Mariane B. ^{[1
]}

Rezende, Victoria L. ^{[1
]}

Rodrigues, Matheus S. ^{[2
]}

Torres, Carolina A. ^{[1
]}

Lemos, Isabela S. ^{[1
]}

Candiotto, Gabriela ^{[1
]}

Gava, Fernanda F. ^{[2
]}

de Oliveira, Jade ^{[3
]}

Valvassori, Samira S. ^{[2
]}

机构：

[1] Univ Extremo Sul Catarinense, Lab Doencas Neurometab, Lab Neurol Expt, Programa Posgrad Ciencias Saude, BR-88806000 Criciuma, SC, Brazil

[2] Univ Extremo Sul Catarinense, Lab Psiquiatria Translac, Programa Posgrad Ciencias Saude, BR-88806000 Criciuma, SC, Brazil

[3] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Biol Bioquim, Dept Bioquim, Inst Ciencias Basicas Saude, BR-90035000 Porto Alegre, RS, Brazil

来源：

METABOLIC BRAIN DISEASE | 2021年 / 36卷 / 02期

关键词：

Maple Syrup Urine Disease; Branched-chain amino acids; Epigenetics; DNA methyltransferase; Histone deacetylases; Histone acetyltransferases; DNA METHYLATION; HISTONE ACETYLATION; MEMORY FORMATION; MECHANISMS; GENE; RATS; MUTATION; NEURONS; IMPACT;

D O I：

10.1007/s11011-020-00631-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder that affects the activity of the branched-chain alpha-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 alpha-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.

引用

页码：247 / 254

页数：8

共 66 条

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