title: Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain.
abstract: Maple syrup urine disease (MSUD) is caused by an inborn error in metabolism resulting from a deficiency in the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. High levels of BCAAs are associated with neurological dysfunction and the role of pro- and mature brain-derived neurotrophic factor (BDNF) in the neurological dysfunction of MSUD is still unclear. Thus, in the present study we investigated the effect of an acute BCAA pool administration on BDNF levels and on the pro-BDNF cleavage-related proteins S100A10 and tissue plasminogen activator (tPA) in rat brains. Our results demonstrated that acute Hyper-BCAA (H-BCAA) exposure during the early postnatal period increases pro-BDNF and total-BDNF levels in the hippocampus and striatum. Moreover, tPA levels were significantly decreased, without modifications in the tPA transcript levels in the hippocampus and striatum. On the other hand, the S100A10 mRNA and S100A10 protein levels were not changed in the hippocampus and striatum. In the 30-day-old rats, we observed increased pro-BDNF, total-BDNF and tPA levels only in the striatum, whereas the tPA and S100A10 mRNA expression and the immunocontent of S100A10 were not altered. In conclusion, we demonstrated that acute H-BCAA administration increases the pro-BDNF/total-BDNF ratio and decreases the tPA levels in animals, suggesting that the BCAA effect may depend, at least in part, on changes in BDNF post-translational processing.
authors: Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil.
authors: Giselli
authors: G
authors: Scaini
authors: Meline O S
authors: MO
authors: Morais
authors: Camila B
authors: CB
authors: Furlanetto
authors: Luiza W
authors: LW
authors: Kist
authors: Talita C B
authors: TC
authors: Pereira
authors: Patrícia F
authors: PF
authors: Schuck
authors: Gustavo C
authors: GC
authors: Ferreira
authors: Matheus A B
authors: MA
authors: Pasquali
authors: Daniel P
authors: DP
authors: Gelain
authors: José Cláudio F
authors: JC
authors: Moreira
authors: Maurício R
authors: MR
authors: Bogo
authors: Emilio L
authors: EL
authors: Streck
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000597:Amino Acids, Branched-Chain; D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor