Mitchell I J, Clarke C E, Boyce S, Robertson R G, Peggs D, Sambrook M A, Crossman A R
Department of Cell and Structural Biology, Medical School, University of Manchester, U.K.
Neuroscience. 1989;32(1):213-26. doi: 10.1016/0306-4522(89)90120-6.
The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism. Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24-27%), the ventral anterior and ventral lateral nuclei of the thalamus (14-22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17-69%). A profound decrease (17-26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus. We propose these data to indicate that in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the projection from the subthalamic nucleus to the globus pallidus; and (v) increased activity in neurons of the medial segment of the globus pallidus projecting to the ventral anterior/ventral lateral thalamus and the pedunculopontine nucleus. These results are compared to the 2-deoxyglucose uptake findings in previous studies from this laboratory in hemiballism and hemichorea in the monkey. The central importance of the subthalamic nucleus in all three conditions is proposed, and supportive evidence for the excitatory nature of subthalamic efferent fibres is adduced.
2-脱氧葡萄糖代谢图谱技术已被用于研究在1-甲基-4-苯基-1,2,3,6-四氢吡啶灵长类帕金森病模型中帕金森综合征症状背后的神经机制。在六只食蟹猴中，1-甲基-4-苯基-1,2,3,6-四氢吡啶要么（a）静脉注射以诱发全身性帕金森综合征，要么（b）注入一侧颈动脉以诱发单侧帕金森综合征。尸检显示，两组分别出现双侧或单侧黑质致密部的严重细胞丢失。此外，接受静脉注射1-甲基-4-苯基-1,2,3,6-四氢吡啶的动物中，腹侧被盖区和蓝斑也有病理改变。与对照组相比，2-脱氧葡萄糖放射自显影显示帕金森病动物大脑中2-脱氧葡萄糖摄取存在广泛变化。这些变化大多发生在基底神经节及其相关结构，且两组实验动物的变化在性质上相似。苍白球外侧段（24 - 27%）、丘脑腹前核和腹外侧核（14 - 22%）以及尾侧中脑的脚桥被盖核（17 - 69%）的2-脱氧葡萄糖摄取显著增加。底丘脑核的2-脱氧葡萄糖摄取则显著下降（17 - 26%）。我们认为这些数据表明，在1-甲基-4-苯基-1,2,3,6-四氢吡啶诱发的帕金森综合征中，基底神经节回路存在以下异常神经元活动模式：（i）从壳核到苍白球外侧段的投射活动增加；（ii）从壳核到苍白球内侧段的投射活动减少；（iii）从苍白球外侧段到底丘脑核的投射活动减少；（iv）从底丘脑核到苍白球的投射活动增加；以及（v）苍白球内侧段投射到腹前/腹外侧丘脑和脚桥核神经元的活动增加。这些结果与本实验室先前关于猴子偏身投掷症和偏身舞蹈症的研究中2-脱氧葡萄糖摄取结果进行了比较。提出了底丘脑核在所有这三种情况中的核心重要性，并给出了支持底丘脑传出纤维具有兴奋性的证据。
