title: Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis.
abstract: Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N-acetyl-aspartyl glutamate and its metabolite, N-acetyl-aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N-acetyl-aspartyl glutamate and N-acetyl-aspartate was decreased by 60% (p less than 0.05) and 40% (p less than 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: J D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: G
authors.initials: G
authors.lastname: Tsai
authors.forename: R W
authors.initials: RW
authors.lastname: Kuncl
authors.forename: L
authors.initials: L
authors.lastname: Clawson
authors.forename: D R
authors.initials: DR
authors.lastname: Cornblath
authors.forename: D B
authors.initials: DB
authors.lastname: Drachman
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: B L
authors.initials: BL
authors.lastname: Stauch
authors.forename: J T
authors.initials: JT
authors.lastname: Coyle
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000378:metabolism; D004151:Dipeptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000134:cerebrospinal fluid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D005971:Glutamates; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate