Role of external pallidal segment in primate parkinsonism: Comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment
Role of external pallidal segment in primate parkinsonism: Comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment
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DOI：
10.1523/jneurosci.0836-04.2004
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发表时间：
2004-07-21
影响因子：
5.3
通讯作者：
Wichmann, T
中科院分区：
文献类型：
--
作者：
Soares, J;Kliem, MA;Wichmann, T
这些实验重新检验了外苍白质节段（GPe）活动减少导致丘脑下核（STN）和内苍白质节段（GPi）神经元放电异常以及帕金森运动体征发展的概念。用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）治疗帕金森病的两只恒河猴的细胞外记录显示，GPe的平均神经元放电率下降，而STN和GPi的平均神经元放电率上升。在MPTP后，三个核的神经元都倾向于振荡放电。此外，STN中的GABA释放（通过微透析测量）减少，表明GPe-STN通路活性降低。最后，GPe和GPi中谷氨酸脱氢酶（GAD）浓度升高，可能分别反映纹状体输入增加和局部轴突侧枝活性增加。令人惊讶的是，STN中的GAD蛋白保持不变，这表明通常认为GAD水平主要由gaba能元件的总体活性决定的假设可能过于简单。将mptp治疗动物的结果与第二组3只伊博滕酸损伤GPe的动物的结果进行比较。GPe病变导致STN和GPi的放电增加，与MPTP后的变化相当，但没有引起振荡性破裂，也没有行为影响。结果表明，单纯的GPe活性降低不会产生帕金森病。其他变化，如STN和GPi放电模式的改变，可能在帕金森病的发生中起重要作用。
These experiments re-examined the notion that reduced activity in the external pallidal segment (GPe) results in the abnormalities of neuronal discharge in the subthalamic nucleus (STN) and the internal pallidal segment (GPi) and in the development of parkinsonian motor signs. Extracellular recording in two rhesus monkeys, which had been rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP), revealed that the average neuronal discharge rate decreased in GPe but increased in STN and GPi. After MPTP, neurons in all three nuclei tended to discharge in oscillatory bursts. In addition, GABA release in STN ( measured with microdialysis) was reduced, indicative of reduced activity along the GPe-STN pathway. Finally, the concentration of glutamic acid dehydrogenase ( GAD; measured with autoimmunoradiography) was increased in GPe and GPi, likely reflecting increased striatal input and increased activity of local axon collaterals, respectively. Surprisingly, GAD protein in STN remained unchanged, indicating that the usual assumption that GAD levels are determined primarily by the overall activity of GABAergic elements may be too simplistic. The results from the MPTP-treated animals were compared with results obtained in a second group of three animals with ibotenic acid lesions of GPe. GPe lesions resulted in increased discharge in STN and GPi, comparable with the changes seen after MPTP but did not induce oscillatory bursting and had no behavioral effects. The results indicate that a mere reduction of GPe activity does not produce parkinsonism. Other changes, such as altered discharge patterns in STN and GPi, may play an important role in the generation of parkinsonism.