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Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain\u2010derived neurotrophic factor (BNDF). We examined both pro\u2010BDNF and <jats:italic>bdnf<\/jats:italic> mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro\u2010BDNF levels. Treatment with N\u2010acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.<\/jats:p>","DOI":"10.1007\/s10545-012-9549-z","type":"journal-article","created":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T21:02:54Z","timestamp":1351544574000},"page":"721-730","source":"Crossref","is-referenced-by-count":29,"title":["Chronic administration of branched\u2010chain amino acids impairs spatial memory and increases brain\u2010derived neurotrophic factor in a rat model"],"prefix":"10.1002","volume":"36","author":[{"given":"Giselli","family":"Scaini","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioenerg\u00e9tica, Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade Universidade do Extremo Sul Catarinense Criciuma SC Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia Translacional em Medicina (INCT\u2010TM) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa M.","family":"Comim","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia Translacional em Medicina (INCT\u2010TM) Porto Alegre RS Brazil"},{"name":"Laborat\u00f3rio de Neuroci\u00eancias, Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade Universidade do Extremo Sul Catarinense Criciuma SC Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna M. 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