EXCITATORY AMINO-ACID BINDING-SITES IN THE CAUDATE-NUCLEUS AND FRONTAL-CORTEX OF HUNTINGTONS-DISEASE
EXCITATORY AMINO-ACID BINDING-SITES IN THE CAUDATE-NUCLEUS AND FRONTAL-CORTEX OF HUNTINGTONS-DISEASE
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DOI：
10.1002/ana.410300607
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发表时间：
1991-12-01
影响因子：
11.2
通讯作者：
PENNEY, JB
中科院分区：
文献类型：
--
作者：
DURE, LS;YOUNG, AB;PENNEY, JB
亨廷顿病是一种显性遗传的进行性神经退行性疾病，会导致基底神经节出现明显的病理变化。选择性神经元死亡的病理生理学尚不清楚，但有证据表明神经毒性可能是由作用于兴奋性氨基酸受体的内源性物质引起的。先前的数据显示，亨廷顿病壳核中与一类谷氨酸受体（N-甲基-D-天冬氨酸（NMDA）受体）的结合选择性减少。本研究旨在使用定量体外放射自显影技术确定亨廷顿病患者和对照受试者尾状核和额叶皮层中所有目前定义的兴奋性氨基酸受体亚群的结合相对密度。 NMDA、MK-801、甘氨酸、红藻氨酸和 α-氨基-3-羟基-5-甲基异恶唑丙酸 (AMPA) 受体结合均降低至相似程度 (50-60%)。与代谢型使君子氨酸受体和非 NMDA、非红藻氨酸、非君子鲨酸 (NNKQ) 位点的结合分别无显着性降低 31% 和 26%。尾状核中 NMDA、MK-801、AMPA、红藻氨酸、代谢型和 NNKQ 受体的放射自显影图显示了不均匀的结合模式，与对照尾状核中观察到的结合模式不同。亨廷顿病患者和对照受试者的额叶皮层与所有受体亚型的结合是相同的。数据表明，亨廷顿病尾状核中没有单一的兴奋性氨基酸受体选择性减少。
Huntington's disease is a dominantly inherited, progressive neurodegenerative disorder causing marked pathology in the basal ganglia. The pathophysiology of the selective neuronal death is as yet unknown, but evidence suggests that the neurotoxicity may result from endogenous substances acting at excitatory amino acid receptors. Previous data have shown a selective decrease in binding to one class of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor in the putamen of Huntington's disease. The present study was undertaken to determine the relative density of binding to all of the currently defined subpopulations of excitatory amino acid receptors in the caudate nuclei and frontal cortex of patients with Huntington's disease and of control subjects, using quantitative in vitro autoradiography. NMDA, MK-801, glycine, kainate, and alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor binding were all decreased to a similar extent (50-60%). Binding to the metabotropic quisqualate receptor and to the non-NMDA, nonkainate, nonquisqualate (NNKQ) site was decreased nonsignificantly by 31% and 26%, respectively. Autoradiograms of NMDA, MK-801, AMPA, kainate, metabotropic, and NNKQ receptors in caudates revealed an inhomogeneous pattern of binding that is different from the binding pattern seen in control caudates. Binding to all receptor subtypes was the same in the frontal cortex from Huntington's disease patients and control subjects. The data suggest that no single excitatory amino acid receptor is selectively decreased in the caudate of Huntington's disease.