Elsevier

Brain Research

Volume 556, Issue 1, 9 August 1991, Pages 151-156
Brain Research

Reductions in acidic amino acids andN-acetylaspartylglutamate in amyotrophic lateral sclerosis CNS

https://doi.org/10.1016/0006-8993(91)90560-IGet rights and content
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Abstract

Acidic excitatory amino acids have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We now report that, in addition to selective regional reductions in endogenous aspartate and glutamate,N-acetylaspartate (NAA), andN-acetylaspartyglutamate (NAAG) are also decreased in the CNS, whereas the activity ofN-acetylated-α-linked-amino dipeptidase (NAALADase) is increased. In cervical cord, the concentrations of aspartate and glutamate were decreased significantly in the ventral horn; NAA was decreased in the ventral horn, dorsal horn and ventral column, whereas NAAG was decreased in all regions of the cord examined, except the posterior column. NAALADase activity was increased in the ventral column. In motor cortex of ALS patients, aspartate and glutamate were decreased and NAALADase activity was increased in both gray and white matter; whereas NAAG was decreased in gray matter alone. None of these parameters was affected in the cerebral cortex of the Huntington's patients. Of the markers examined, the alterations in the levels of NAAG most closely parallel the cellular neuropathology in ALS.

Keywords

Amyotrophic lateral sclerosis
Aspartate
Glutamate
N-Acetylaspartate
N-Acetylaspartylglutamate
N-Acetylate-α-linked-amino dipeptidase (NAALADase)
Excitoxin

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This research was supported by the McKnight Foundation, the Muscular Dystrophy Association, the Jay Slotkin Fund for Neuromuscular Research, and a USPHS Grant NS-13584. We thank Alice Trawinski for her editorial assistance.