Branched-chain amino acids induce neurotoxicity in rat cortical cultures.
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.
Contrusciere
Valentina
V
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Paradisi
Silvia
S
Matteucci
Andrea
A
Malchiodi-Albedi
Fiorella
F
D000597:Amino Acids, Branched-Chain / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000597:Amino Acids, Branched-Chain; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; C493395:Slc1a2 protein, rat; D016291:Dizocilpine Maleate; D005974:Glutamate-Ammonia Ligase