Branched-Chain Amino Acids Induce Neurotoxicity in Rat Cortical Cultures

被引:33
作者
Contrusciere, Valentina [1 ]
Paradisi, Silvia [1 ]
Matteucci, Andrea [1 ]
Malchiodi-Albedi, Fiorella [1 ]
机构
[1] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy
关键词
Branched-chain amino acids; Valine; Excitotoxicity; Amyotrophic lateral sclerosis; Primary neuronal cultures; Astrocytes; AMYOTROPHIC-LATERAL-SCLEROSIS; GLIAL-CELLS; METABOLISM; ASTROCYTES; DISEASES;
D O I
10.1007/s12640-009-9115-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The higher risk for amyotrophic lateral sclerosis (ALS) among professional soccer players, recently reported in Italy, has stimulated investigations in the search for environmental factors that may be at the origin of the increased susceptibility to the disease. Here we studied if high concentrations of branched-chain amino acids (BCAAs), widely used among athletes as dietary integrators to improve physical performance, may be related to an excitotoxic neuronal cell damage. Our results show that (i) high concentrations of BCAAs are neurotoxic and increase excitotoxicity in cortical neurons; (ii) neurotoxicity is brain area specific, being detected in cortical, but not in hippocampal neurons; (iii) it is related to NMDA receptor overstimulation, since it is abolished in the presence of MK-801, a specific NMDA channel blocker; (iv) it depends on the presence of astrocytes. We describe here a possible biological link between an environmental factor (high dietary intake of BCAAs) and the increased risk of ALS among soccer players.
引用
收藏
页码:392 / 398
页数:7
相关论文
共 21 条
[1]   Football increases the risk for Lou Gehrig's disease, amyotrophic lateral sclerosis [J].
Abel, Ernest L. .
PERCEPTUAL AND MOTOR SKILLS, 2007, 104 (03) :1251-1254
[2]   Among the branched-chain amino acids, only valine metabolism is up-regulated in astrocytes during glutamate exposure [J].
Bak, Lasse K. ;
Johansen, Maja L. ;
Schousboe, Arne ;
Waagepetersen, Helle S. .
JOURNAL OF NEUROSCIENCE RESEARCH, 2007, 85 (15) :3465-3470
[3]   Proportionate mortality of Italian soccer players: Is amyotrophic lateral sclerosis an occupational disease? [J].
Belli, S ;
Vanacore, N .
EUROPEAN JOURNAL OF EPIDEMIOLOGY, 2005, 20 (03) :237-242
[4]   Cellular distribution of branched-chain amino acid aminotransferase isoenzymes among rat brain glial cells in culture [J].
Bixel, MG ;
Hutson, SM ;
Hamprecht, B .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1997, 45 (05) :685-694
[5]   GLUTAMATE NEUROTOXICITY AND DISEASES OF THE NERVOUS-SYSTEM [J].
CHOI, DW .
NEURON, 1988, 1 (08) :623-634
[6]  
Davis JM, 2000, AM J CLIN NUTR, V72, p573S, DOI 10.1093/ajcn/72.2.573S
[7]   Branched-chain amino acids and brain function [J].
Fernstrom, JD .
JOURNAL OF NUTRITION, 2005, 135 (06) :1539S-1546S
[8]   Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain [J].
Fernstrom, John D. ;
Fernstrom, Madelyn H. .
JOURNAL OF NUTRITION, 2007, 137 (06) :1539S-1547S
[9]   Brached-chain amino acid metabolism: Implications for establishing safe intakes' [J].
Hutson, SM ;
Sweatt, AJ ;
LaNoue, KF .
JOURNAL OF NUTRITION, 2005, 135 (06) :1557S-1564S
[10]   Nitrogen shuttling between neurons and glial cells during glutamate synthesis [J].
Lieth, E ;
LaNoue, KF ;
Berkich, DA ;
Xu, BY ;
Ratz, M ;
Taylor, C ;
Hutson, SM .
JOURNAL OF NEUROCHEMISTRY, 2001, 76 (06) :1712-1723