Nisbet A P, Eve D J, Kingsbury A E, Daniel S E, Marsden C D, Lees A J, Foster O J
Parkinson's Disease Society Brain Bank, London, U.K.
Neuroscience. 1996 Nov;75(2):389-406. doi: 10.1016/0306-4522(96)00299-0.
Expression of glutamate decarboxylase-67 messenger RNA was examined in the basal ganglia of normal controls and of cases of Parkinson's disease using in situ hybridization histochemistry in human post mortem material. In controls glutamate decarboxylase-67 messenger RNA expression was detected in all large neurons in both segments of the globus pallidus and in three neuronal subpopulations in the striatum as well as in substantia nigra reticulata neurons and in a small sub-population of subthalamic neurons. In Parkinson's disease, there was a statistically significant decrease of 50.7% in glutamate decarboxylase-67 messenger RNA expression per neuron in the lateral segment of the globus pallidus (controls: mean 72.8 microns2 +/- S.E.M. 8.7 of silver grain/neuron, n = 12; Parkinson's disease: mean 35.9 microns2 +/- S.E.M. 9.7 of silver grain/neuron, n = 9, P = 0.01, Student's t-test). In the medial segment of the globus pallidus, there was a small, but non-significant decrease of glutamate decarboxylase-67 messenger RNA expression in Parkinson's disease (controls: mean 100.6 microns2 +/- S.E.M. 7.2 of silver grain/neuron, n = 11; Parkinson's disease: mean 84.8 microns2 +/- S.E.M. 13.0 of silver grain/neuron, n = 7, P = 0.1, Student's t-test). No significant differences in glutamate decarboxylase-67 messenger RNA were detected in striatal neuronal sub-populations between Parkinson's disease cases and controls. These results are the first direct evidence in humans that there is increased inhibitory drive to the lateral segment of the globus pallidus in Parkinson's disease, as suggested by data from animal models. We therefore provide theoretical support for current experimental neurosurgical approaches to Parkinson's disease.
运用原位杂交组织化学技术，在人类尸检材料中检测了正常对照者及帕金森病患者基底神经节中谷氨酸脱羧酶-67信使核糖核酸（glutamate decarboxylase-67 messenger RNA，GAD67 mRNA）的表达。在对照者中，苍白球两个节段的所有大神经元、纹状体的三个神经元亚群、黑质网状部神经元以及一小部分丘脑底核神经元中均检测到GAD67 mRNA表达。在帕金森病患者中，苍白球外侧节段单个神经元的GAD67 mRNA表达量有统计学意义的显著下降，下降了50.7%（对照者：平均每神经元银颗粒72.8平方微米±标准误8.7，n = 12；帕金森病患者：平均每神经元银颗粒35.9平方微米±标准误9.7，n = 9，P = 0.01，Student t检验）。在苍白球内侧节段，帕金森病患者的GAD67 mRNA表达有轻微下降，但无统计学意义（对照者：平均每神经元银颗粒100.6平方微米±标准误7.2，n = 11；帕金森病患者：平均每神经元银颗粒84.8平方微米±标准误13.0，n = 7，P = 0.1，Student t检验）。帕金森病患者与对照者的纹状体神经元亚群中，未检测到GAD67 mRNA有显著差异。这些结果首次在人类中直接证明，正如动物模型数据所提示的，帕金森病中苍白球外侧节段的抑制性驱动增强。因此，我们为当前针对帕金森病的实验性神经外科治疗方法提供了理论支持。
