Eriksson H, Mägiste K, Plantin L O, Fonnum F, Hedström K G, Theodorsson-Norheim E, Kristensson K, Stålberg E, Heilbronn E
Unit of Neurochemistry and Neurotoxicology, University of Stockholm, Sweden.
Arch Toxicol. 1987;61(1):46-52. doi: 10.1007/BF00324547.
Four monkeys were exposed to a total of 8 g each of 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 globus 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.(ABSTRACT TRUNCATED AT 250 WORDS)
四只猴子在5个月内通过反复皮下注射，每只总共接触了8克氧化锰，之后在处死前让它们存活1周-6个月。约2个月后，所有动物都出现了多动行为。接触开始约5个月后，动物变得活动减少，步态不稳，随后部分动物出现动作性震颤。动物的上肢和下肢均无力，手脚动作非常笨拙。接触期间，血清锰含量升高了10-40倍，脑中的含量一般增加了10倍以上，苍白球和壳核中的含量最高。观察到的神经化学效应在苍白球和壳核中也最为明显。在这些区域，多巴胺和3,4-二羟基苯乙酸大量减少，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，而其他区域未观察到。这与最近对一名慢性锰中毒患者的神经病理学研究结果[Yamada等人（1986年）《神经病理学学报》70:273-278]一致，该研究中苍白球没有神经元细胞，而黑质中色素细胞的含量正常。我们的数据表明多巴胺能神经末梢数量减少，因为多巴胺合成酶多巴脱羧酶的活性也降低了。（摘要截短于250字）
