Tsai G C, Stauch-Slusher B, Sim L, Hedreen J C, Rothstein J D, Kuncl R, Coyle J T
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Brain Res. 1991 Aug 9;556(1):151-6. doi: 10.1016/0006-8993(91)90560-i.
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), and N-acetylaspartylglutamate (NAAG) are also decreased in the CNS, whereas the activity of N-acetylated-alpha-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.
酸性兴奋性氨基酸已被认为与肌萎缩侧索硬化症（ALS）的发病机制有关。我们现在报告，除了内源性天冬氨酸和谷氨酸的选择性区域减少外，中枢神经系统中的N-乙酰天门冬氨酸（NAA）和N-乙酰天门冬氨酰谷氨酸（NAAG）也减少，而N-乙酰化-α-连接氨基酸二肽酶（NAALADase）的活性增加。在颈髓中，腹角的天冬氨酸和谷氨酸浓度显著降低；腹角、背角和腹侧柱中的NAA减少，而在所检查的脊髓所有区域中，除后柱外，NAAG均减少。腹侧柱中的NAALADase活性增加。在ALS患者的运动皮层中，灰质和白质中的天冬氨酸和谷氨酸均减少，NAALADase活性增加；而仅灰质中的NAAG减少。这些参数在亨廷顿病患者的大脑皮层中均未受影响。在所检查的标志物中，NAAG水平的变化与ALS中的细胞神经病理学最为密切相关。
