title: The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.
abstract: Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan. Electronic address: dwsako@yahoo.co.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sako
authors.affiliation: Department of Radiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Radiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D016923:Cell Death; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism*; D009474:Neurons / Q000473:pathology
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: Amyotrophic lateral sclerosis; Excitotoxicity; Glutamate; Magnetic resonance spectroscopy; N-acetyl aspartate; Primary motor cortex