Amino acids acting as transmitters in amyotrophic lateral sclerosis (ALS)

Objective - In amyotrophic lateral sclerosis (ALS), a neurodegenerative dis ease of unknown origin, excitotoxic mechanisms are supposed to be involved. Divergent results are, however, presented either because of the heterogene ity of this disease, and/or different methodologies used to evaluate the ex citotoxic amino acids content. The results of the most sensitive high perfo rmance liquid chromatography (HPLC) techniques with precolumn derivatizatio n of fasting serum and CSF glutamate, aspartate, glycine and gamma-aminobut yric acid (GABA) in mild and severely progressing ALS cases are presented h ere. Material and methods - We studied 25 ALS patients with different cours e of the disease and controls, which consisted of 10 cases with other motor neuron diseases and 20 healthy, age-matched subjects. Results - In the ALS patients with a mild course of the disease serum glutamate and aspartate c ontent was either normal or slightly decreased, in all of these cases a ris e in GABA and glycine was present. In the severely progressing ALS cases se rum glutamate and aspartate was increased. The GABA content was either norm al or increased, the glycine level appeared to be either normal or decrease d. In CSF the amino acids changes in ALS were less pronounced as compared t o serum. The most frequent finding was the increase in GABA concentration b oth in the mild and the severely progressing group. CSF glutamate in ALS pa tients with mild course of the disease was decreased, in the severely progr essing cases the glutamate level appeared in a broad range from decreased t o increased values. CSF aspartate was either normal or elevated, glycine va lues were present in a broad range from decreased to increased values. In t he other tested motor neuron diseases no consistent changes in serum and CS F amino acids concentration was observed. Conclusions - The data from serum and CSF indicate that in ALS an imbalance between excitatory and inhibitor y amino acids might be present in the brain, which may be induced in differ ent ways in particular ALS patients. It may be an important factor for the mediation of neurons death.