Evaluation of Acetylcholinesterase in an Animal Model of Maple Syrup Urine Disease Giselli Scaini & Natália de Rochi & Isabela C. Jeremias & Pedro F. Deroza & Alexandra I. Zugno & Talita C. B. Pereira & Giovanna M. T. Oliveira & Luiza W. Kist & Maurício R. Bogo & Patrícia F. Schuck & Gustavo C. Ferreira & Emilio L. Streck Received: 4 November 2011 / Accepted: 1 February 2012 / Published online: 12 February 2012 # Springer Science+Business Media, LLC 2012 Abstract Maple syrup urine disease is an inherited meta- bolic disease predominantly characterized by neurological dysfunction. However, the mechanisms underlying the neu- ropathology of this disease are still not defined. Therefore, the aim of this study was to investigate the effect of acute and chronic administration of a branched-chain amino acids (BCAA) pool (leucine, isoleucine, and valine) on acetylcho- linesterase (AChE) activity and gene expression in the brain and serum of rats and to assess if antioxidant treatment prevented the alterations induced by BCAA administration. Our results show that the acute administration of a BCAA pool in 10- and 30-day-old rats increases AChE activity in the cerebral cortex, striatum, hippocampus, and serum. Moreover, chronic administration of the BCAA pool also increases AChE activity in the structures studied, and anti- oxidant treatment prevents this increase. In addition, we show a significant decrease in the mRNA expression of AChE in the hippocampus following acute administration in 10- and 30-day-old rats. On the other hand, AChE ex- pression increased significantly after chronic administration of the BCAA pool. Interestingly, the antioxidant treatment was able to prevent the increased AChE activity without altering AChE expression. In conclusion, the results from the present study demonstrate a marked increase in AChE activity in all brain structures following the administration of a BCAA pool. Moreover, the increased AChE activity is prevented by the coadministration of N-acetylcysteine and deferoxamine as antioxidants. Keywords Maple syrup urine disease . Branched chain amino acids . Antioxidant treatment . Acetylcholinesterase . mRNA levels Introduction Maple syrup urine disease (MSUD) is an inherited metabol- ic disorder caused by a severe deficiency in branched-chain α-keto acid dehydrogenase complex (E.C. 1.2.4.4) activity. The metabolic defect leads to an accumulation of the branched-chain amino acids (BCAA) leucine (Leu), isoleu- cine (Ile), and valine (Val) and the corresponding branched- chain α-keto acids, α-ketoisocaproic acid, α-keto- β- G. Scaini : N. de Rochi : I. C. Jeremias : E. L. Streck Laboratório de Bioenergética, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma 88806-000 Santa Catarina, Brazil G. Scaini : N. de Rochi : I. C. Jeremias : P. F. Deroza : A. I. Zugno : T. C. B. Pereira : G. M. T. Oliveira : L. W. Kist : M. R. Bogo : E. L. Streck (*) Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, Rio Grande de Sul, Brazil e-mail: emiliostreck@gmail.com P. F. Deroza : A. I. Zugno Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil T. C. B. Pereira : G. M. T. Oliveira : L. W. Kist : M. R. Bogo 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, Brazil P. F. Schuck : G. C. Ferreira Laboratório de Erros Inatos do Metabolismo, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil Mol Neurobiol (2012) 45:279–286 DOI 10.1007/s12035-012-8243-3