In vitro neurotoxic properties and excitatory aminoacids concentration in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Relationship with the degree of certainty of disease diagnoses.
OBJECTIVE
To determine glutamate and aspartate levels in the cerebrospinal fluid (CSF) in patients with sporadic amyotrophic lateral sclerosis (SALS) grouped according to El Escorial diagnostic criteria, and to perform an in vitro assessment of the neurotoxicity of the CSF in murine cortical neurons.


METHODS
SALS patients were sorted according to El Escorial diagnostic criteria. Glutamate and aspartate were measured in the CSF using high performance liquid chromatography. Cultured cortical neuron viability was determined after exposure to CSF for 24 h.


RESULTS
Glutamate levels were elevated in 28 out of the 29 patients with definite, probable or possible SALS. There were no differences in glutamate concentrations when the three clinical forms of the disease were compared; neither there were significant variation across disease duration and clinical presentation. In agreement with previous reports, we concluded that CSF-SALS-induced in vitro neurotoxicity is mediated by ionotropic glutamate receptors. We found no relationship between the degree of in vitro neurotoxicity and glutamate concentration in the CSF.


CONCLUSIONS
Glutamate but not aspartate CSF levels may contribute to ALS pathogenesis. However, glutamate levels may not influence the degree of diagnosis certainty or lesion extension.
Instituto de Investigaciones Farmacológicas-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina. Monica.Fiszman@fda.hhs.gov
M L
ML
Fiszman
K C
KC
Ricart
A
A
Latini
G
G
Rodríguez
R E P
RE
Sica
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D000818:Animals; D001224:Aspartic Acid / Q000134:cerebrospinal fluid*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D013997:Time Factors
D001224:Aspartic Acid; D018698:Glutamic Acid