title: A chemically-induced acute model of maple syrup urine disease in rats for neurochemical studies.
abstract: We report a chemically-induced model of maple syrup urine disease (MSUD) in 10- and 30-day-old rats produced by subcutaneous administration of a branched-chain amino acids (BCAA) pool along with the analyses of plasma and brain amino acid levels by HPLC at 0-120 min after administration. We observed an increase of plasma leucine (Leu), isoleucine (Ile) and valine (Val) concentrations in both 10- and 30-day-old rats. These increases were accompanied by a concomitant reduction of plasma concentrations of methionine (Met), phenylalanine (Phe), tyrosine (Tyr), histidine (His), alanine (Ala), lysine (Lys), and ornithine (Orn) in 10-day-old rats and of Met, Phe, Tyr, tryptophan (Trp), and Orn in 30-day-old rats. These results are similar to those observed in MSUD patients during crises, when plasma levels of large neutral amino acids (LNAA) are also reduced when BCAA concentrations are increased. In the brain, increased concentrations of Leu, Ile and Val were achieved in 10-day-old rats at all times after injection. In contrast, no differences in cerebral concentrations of BCAA were observed in 30-day-old rats. In conclusion, the present MSUD model, using 10- rather than 30-day-old rats, has a similar amino acid profile to that of MSUD untreated patients and is suitable to investigate the mechanisms of brain damage characteristic of this disorder.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bridi
authors.forename: Fernanda U
authors.initials: FU
authors.lastname: Fontella
authors.forename: Vânia
authors.initials: V
authors.lastname: Pulrolnik
authors.forename: César A
authors.initials: CA
authors.lastname: Braun
authors.forename: Giovanni K
authors.initials: GK
authors.lastname: Zorzi
authors.forename: Daniella
authors.initials: D
authors.lastname: Coelho
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004563:Electrochemistry / Q000379:methods; D008297:Male; D008375:Maple Syrup Urine Disease / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain