Comings D E, Goetz I E, Holden J, Holtz J
Am J Hum Genet. 1981 Mar;33(2):175-86.
Injection of kainic acid, a rigid analog of the excitatory neurotransmitter glutamic acid (glu), into the neostriatum of rats produces a condition that mimics Huntington disease (HD) in at least 12 different morphological and biochemical parameters. These results suggested that one of the possible basic mechanisms in HD is a defect in the presynaptic of glial uptake of glu, resulting in chronic hyperstimulation and death of a specific set of neurons. To test this hypothesis, the uptake of glu was studied in 12 carefully matched sets of control-HD pairs and two lines of Tourette syndrome fibroblasts. Although the first six sets suggested a glutamate transport defect in HD cells, examination of 12 sets indicated that there were no significant differences between control and HD cells. The fibroblasts showed both a high and low affinity uptake of glutamic acid. Sodium dependent uptake of L-glutamate (L-glu) minus D-glutamate (D-glu) at 100, 1,000, and 10,000 Micrometers glutamate was normal in HD and Tourette syndrome cells.
向大鼠新纹状体注射兴奋性神经递质谷氨酸(glu)的刚性类似物海藻酸,会产生一种在至少12个不同形态学和生物化学参数方面模拟亨廷顿病(HD)的病症。这些结果表明,HD可能的基本机制之一是神经胶质细胞对glu的突触前摄取存在缺陷,导致特定一组神经元的慢性过度刺激和死亡。为了验证这一假设,在12组精心匹配的对照-HD对以及两株图雷特综合征成纤维细胞中研究了glu的摄取情况。尽管前六组表明HD细胞存在谷氨酸转运缺陷,但对12组的检查表明,对照细胞和HD细胞之间没有显著差异。成纤维细胞对谷氨酸表现出高亲和力和低亲和力摄取。在HD细胞和图雷特综合征细胞中,100、1000和10000微摩尔谷氨酸浓度下,L-谷氨酸(L-glu)减去D-谷氨酸(D-glu)的钠依赖性摄取是正常的。