EFFECTS OF LOCUS-COERULEUS LESIONS ON PARKINSONIAN SIGNS, STRIATAL DOPAMINE AND SUBSTANTIA-NIGRA CELL LOSS AFTER 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN MONKEYS - A POSSIBLE ROLE FOR THE LOCUS-COERULEUS IN THE PROGRESSION OF PARKINSONS-DISEASE
EFFECTS OF LOCUS-COERULEUS LESIONS ON PARKINSONIAN SIGNS, STRIATAL DOPAMINE AND SUBSTANTIA-NIGRA CELL LOSS AFTER 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN MONKEYS - A POSSIBLE ROLE FOR THE LOCUS-COERULEUS IN THE PROGRESSION OF PARKINSONS-DISEASE
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DOI：
10.1016/0306-4522(91)90345-o
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发表时间：
1991-01-01
期刊：
影响因子：
3.3
通讯作者：
COLPAERT, FC
中科院分区：
文献类型：
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作者：
MAVRIDIS, M;DEGRYSE, AD;COLPAERT, FC
6对雌性松鼠猴每天腹腔注射1-甲基-4-苯基- 1,2,3,6 -四氢吡啶（MPTP），持续9-14天，从接受双侧6-羟多巴胺损伤或假蓝斑损伤的同一天开始。假手术动物出现了典型的帕金森症状（即震颤、运动迟缓、运动不足和眨眼频率减少），这些症状在MPTP治疗开始后的6至9周内基本恢复。在第9周，这些动物死后纹状体多巴胺水平部分下降（45%），而且这只是在壳核，与3只未手术的正常对照动物相比。此外，组织学检查显示黑质致密部神经元细胞体中度丢失。与之形成鲜明对比的是，蓝斑受损的猴子在MPTP诱导的帕金森症状中几乎没有恢复。这些动物的死后检查显示，所有动物的尾状核（84%）和壳核（91%）多巴胺含量都大幅下降，黑质致密部的神经元细胞严重丢失。这些神经学、生化和组织学评估表明，蓝斑损伤损害了松鼠猴通常发生在MPTP诱导的帕金森症状后的恢复。这些结果支持了蓝斑去肾上腺素能机制缺陷是帕金森病发展的基础的假设。
Six pairs of female squirrel monkeys were given a daily intraperitoneal injection of 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) for 9-14 days, beginning the same day on which they received either a bilateral 6-hydroxydopamine lesion or a sham lesion of the locus coeruleus. Sham animals developed typical parkinsonian signs (i.e. tremor, bradykinesia, hypokinesia and reduced blink rate) which largely recovered by six to nine weeks after the start of MPTP treatment. At nine weeks, post mortem levels of striatal dopamine in these same animals were partially reduced (by 45%), and this only in the putamen, compared to values obtained from three non-operated, normal control animals. Additionally, histological examination revealed a moderate loss of neuronal cell bodies in the substantia nigra, pars compacta. In marked contrast, the locus coeruleus-lesioned monkeys exhibited little or no recovery from the parkinsonian signs induced by MPTP. Post mortem examination of these animals revealed profound decreases in caudate (by 84%) and putamen (by 91%) dopamine content, and severe neuronal cell loss in the substantia nigra pars compacta of all animals.These neurological, biochemical and histological assessments indicate that lesioning of the locus coeruleus impairs the recovery which usually occurs from the parkinsonian manifestations induced by MPTP in squirrel monkeys. The results support the hypothesis that deficient locus coeruleus noradrenergic mechanisms underlie the progression of Parkinson's disease.