EFFECTS OF MANGANESE OXIDE ON MONKEYS AS REVEALED BY A COMBINED NEUROCHEMICAL, HISTOLOGICAL AND NEUROPHYSIOLOGICAL EVALUATION
EFFECTS OF MANGANESE OXIDE ON MONKEYS AS REVEALED BY A COMBINED NEUROCHEMICAL, HISTOLOGICAL AND NEUROPHYSIOLOGICAL EVALUATION
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DOI：
10.1007/bf00324547
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发表时间：
1987-10-01
影响因子：
6.1
通讯作者：
HEILBRONN, E
中科院分区：
文献类型：
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作者：
ERIKSSON, H;MAGISTE, K;HEILBRONN, E
在5个月期间，通过重复皮下注射，将4只猴子暴露于总计8 g锰氧化物，之后将它们放置1周至6个月，然后将它们处死。所有动物在约2个月后出现多动行为。暴露开始后约5个月，动物活动减退，步态不稳，随后一些动物出现动作性震颤。这些动物的上下肢都失去了力量，手脚的动作非常笨拙。血清锰含量随染毒时间增加10-40倍，脑中锰含量普遍增加10倍以上，以苍白球和壳核中锰含量最高。所观察到的神经化学效应也是最大的苍白球和壳核。在这些地区有一个相当大的消耗多巴胺和3，4-二羟基苯乙酸，而高香草酸含量几乎保持不变。在苍白球中观察到严重的神经元细胞丢失，但在其他区域未观察到。这与最近对患有慢性锰中毒的人的神经病理学研究的结果一致[Yamada等（1986）Acta Neuropathol 70：273 - 278]，其中苍白球缺乏神经元细胞，而黑质中的色素细胞含量正常。我们的数据表明多巴胺能神经末梢的数量减少，因为多巴胺合成酶多巴脱羧酶的活性也降低了。除了对多巴胺能系统的影响外，在壳核和苍白球中观察到5-羟基吲哚乙酸含量降低。此外，神经降压素，与多巴胺能系统的功能连接的神经肽，被发现在壳核减少。值得注意的是，在壳核中观察到的所有神经化学作用在尾状核中或多或少都不存在。这些意见进行了讨论，在帕金森病和MPTP病变的大脑中发现了什么。
Four monkeys were exposed to a total of 8 g each for manganese as oxide by repetitive subcutaneous injections during 5 months, after which they were left for 1 week to 6 months before they were sacrificed. All animals developed hyperactive behaviour after about 2 months. About 5 months after the start of the exposure the animals became hypoactive with an unsteady gait, and subsequently an action tremor appeared in some of the animals. The animals lost power in both upper and lower limbs and the movements of the hands and feet were very clumsy. The serum content of manganese rose 10-40 times during the exposure time and the content in brain was generally increased more than 10 times, with the highest content found in globus pallidus and putamen. The observed neurochemical effects were also largest in globus pallidus and putamen. In these regions there was a considerable depletion of dopamine and 3,4-dihydroxyphenylacetic acid, while the homovanillic acid content remained almost unchanged. A severe neuronal cell loss was observed in globulus pallidus but not in other regions. This is in accordance with results from the most recent neuropathological study of a human suffering from chronic manganese poisoning [Yamada et al. (1986) Acta Neuropathol 70: 273-278] where globus pallidus was devoid of neuronal cells while the content of pigmented cells in substantia nigra was normal. Our data suggest a reduction in number of dopaminergic nerve terminals, as the activity of the dopamine synthesizing enzyme DOPA-decarboxylase was also lowered. In addition to the effects on the dopaminergic system, a reduced content of 5-hydroxyindole acetic acid was observed in the putamen and globus pallidus. Moreover neurotensin, a neuropeptide with functional connection to the dopaminergic system, was found to be reduced in the putamen. It was remarkable that all the neurochemical effects seen in the putamen were more or less absent from the caudate nucleus. These observations are discussed in relation to what has been found in Parkinsonian and MPTP-lesioned brains.