Tags

Type your tag names separated by a space and hit enter

Reduction of glutamate uptake into cerebral cortex of developing rats by the branched-chain alpha-keto acids accumulating in maple syrup urine disease.
Neurochem Res. 2004 Apr; 29(4):747-53.NR

Abstract

In the current study we investigated the effect of the branched-chain alpha-keto acids (BCKA) co-ketoisocaproic (KIC), alpha-keto-beta-methylvaleric (KMV), and alpha-ketoisovaleric (KIV) acids, which accumulate in maple syrup urine disease (MSUD), on the in vitro uptake of [3H]glutamate by cerebral cortical slices from rats aged 9, 21, and 60 days of life. We initially observed that glutamate uptake into cerebral cortex of 9- and 21-day-old rats was significantly higher, as compared to that of 60-day-old rats. Furthermore, KIC inhibited this uptake by tissue slices at all ages studied, whereas KMV and KIV produced the same effect only in cortical slices of 21- and 60-day-old rats. Kinetic assays showed that KIC significantly inhibited glutamate uptake in the presence of high glutamate concentrations (50 microM and greater). We also verified that the reduction of glutamate uptake was not due to cellular death, as evidenced by tetrazolium salt and lactate dehydrogenase viability tests of cortical slices in the presence of the BCKA. It is therefore presumed that the reduced glutamate uptake caused by the BCKA accumulating in MSUD may lead to higher extracellular glutamate levels and potentially to excitotoxicity, which may contribute to the neurological dysfunction of the affected individuals.

Authors+Show Affiliations

Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica. Porto Alegre, RS, Brasil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15098937

Citation

Funchal, Cláudia, et al. "Reduction of Glutamate Uptake Into Cerebral Cortex of Developing Rats By the Branched-chain Alpha-keto Acids Accumulating in Maple Syrup Urine Disease." Neurochemical Research, vol. 29, no. 4, 2004, pp. 747-53.
Funchal C, Rosa AM, Wajner M, et al. Reduction of glutamate uptake into cerebral cortex of developing rats by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. Neurochem Res. 2004;29(4):747-53.
Funchal, C., Rosa, A. M., Wajner, M., Wofchuk, S., & Pureur, R. P. (2004). Reduction of glutamate uptake into cerebral cortex of developing rats by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. Neurochemical Research, 29(4), 747-53.
Funchal C, et al. Reduction of Glutamate Uptake Into Cerebral Cortex of Developing Rats By the Branched-chain Alpha-keto Acids Accumulating in Maple Syrup Urine Disease. Neurochem Res. 2004;29(4):747-53. PubMed PMID: 15098937.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of glutamate uptake into cerebral cortex of developing rats by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. AU - Funchal,Cláudia, AU - Rosa,Aline Meyer, AU - Wajner,Moacir, AU - Wofchuk,Susana, AU - Pureur,Regina Pessoa, PY - 2004/4/22/pubmed PY - 2004/6/4/medline PY - 2004/4/22/entrez SP - 747 EP - 53 JF - Neurochemical research JO - Neurochem Res VL - 29 IS - 4 N2 - In the current study we investigated the effect of the branched-chain alpha-keto acids (BCKA) co-ketoisocaproic (KIC), alpha-keto-beta-methylvaleric (KMV), and alpha-ketoisovaleric (KIV) acids, which accumulate in maple syrup urine disease (MSUD), on the in vitro uptake of [3H]glutamate by cerebral cortical slices from rats aged 9, 21, and 60 days of life. We initially observed that glutamate uptake into cerebral cortex of 9- and 21-day-old rats was significantly higher, as compared to that of 60-day-old rats. Furthermore, KIC inhibited this uptake by tissue slices at all ages studied, whereas KMV and KIV produced the same effect only in cortical slices of 21- and 60-day-old rats. Kinetic assays showed that KIC significantly inhibited glutamate uptake in the presence of high glutamate concentrations (50 microM and greater). We also verified that the reduction of glutamate uptake was not due to cellular death, as evidenced by tetrazolium salt and lactate dehydrogenase viability tests of cortical slices in the presence of the BCKA. It is therefore presumed that the reduced glutamate uptake caused by the BCKA accumulating in MSUD may lead to higher extracellular glutamate levels and potentially to excitotoxicity, which may contribute to the neurological dysfunction of the affected individuals. SN - 0364-3190 UR - https://www.unboundmedicine.com/medline/citation/15098937/Reduction_of_glutamate_uptake_into_cerebral_cortex_of_developing_rats_by_the_branched_chain_alpha_keto_acids_accumulating_in_maple_syrup_urine_disease_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=15098937.ui DB - PRIME DP - Unbound Medicine ER -