Niebroj-Dobosz I, Janik P, Mickielewicz A, Jamrozik Z, Kwieciński H
Katedra i Klinika Neurologii AM w Warszawie.
Neurol Neurochir Pol. 2001;35(1 Suppl):81-9.
One of the hypotheses in amyotrophic lateral sclerosis (ALS) indicates on excitatory amino acids as the cause of neuronal death. Changes in their concentration in the tissues and body fluids may be the consequence of a defect in their transport, as well as abnormal activities of glutamate metabolizing enzymes. Abnormal synthesis/degradation of these enzymes and/or influence of activators/inhibitors should be taken into account. The activity of enzymes of glutamate metabolism of rat spinal cord in vitro in the presence of serum and cerebrospinal fluid (CSF) of 20 patients with ALS and 20 healthy controls was tested. In the presence of serum of the ALS patients glutaminase was significantly stimulated, instead of being inhibited; the inhibition of GABA aminotransferase, glutamate decaboxylase and aspartate aminotransferase was less evident than in the controls, glutamate dehydrogenase lost its activity more than in control conditions, the inhibition of glutamine synthetase was comparable to that when normal serum was applied. The activity of the enzymes in the presence of CSF of ALS patients was generally similar to that of normal CSF, except of glutaminase which was stimulated and GABA aminotransferase, which was inhibited stronger than in the presence of normal CSF. This study indicates, that changes in glutamate concentration in tissues and body fluids in ALS may be caused, at least partly, by abnormalities in the activity of glutamate metabolism enzymes, which are in turn induced by neurotoxic agents present in body fluids of ALS patients.
肌萎缩侧索硬化症(ALS)的假说之一认为,兴奋性氨基酸是神经元死亡的原因。其在组织和体液中浓度的变化可能是转运缺陷以及谷氨酸代谢酶异常活性的结果。应考虑这些酶的异常合成/降解和/或激活剂/抑制剂的影响。在20例ALS患者和20例健康对照者的血清和脑脊液(CSF)存在的情况下,测试了大鼠脊髓谷氨酸代谢酶的体外活性。在ALS患者血清存在的情况下,谷氨酰胺酶受到显著刺激,而非抑制;与对照组相比,γ-氨基丁酸转氨酶、谷氨酸脱羧酶和天冬氨酸转氨酶的抑制作用不那么明显,谷氨酸脱氢酶活性丧失比对照条件下更严重,谷氨酰胺合成酶的抑制作用与使用正常血清时相当。在ALS患者脑脊液存在的情况下,这些酶的活性总体上与正常脑脊液相似,但谷氨酰胺酶受到刺激,γ-氨基丁酸转氨酶的抑制作用比在正常脑脊液存在时更强。这项研究表明,ALS患者组织和体液中谷氨酸浓度的变化可能至少部分是由谷氨酸代谢酶活性异常引起的,而这些异常又是由ALS患者体液中存在的神经毒性物质诱导的。