Fujii T, Ito M, Tsuda H, Mikawa H
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
J Neurochem. 1990 Sep;55(3):885-9. doi: 10.1111/j.1471-4159.1990.tb04574.x.
Hemizygous mottled brindled mice (Mobr/y mice) were treated by subcutaneous injection of copper and were decapitated on postnatal day 14. Cytochrome c oxidase (COX) activity of the brain mitochondria in the mice given 10 micrograms of copper/g on day 4 or 7 showed significant increases compared with that of untreated Mobr/y animals, and these mice had no neurological symptoms. Mice given 10 micrograms of copper/g on day 12 showed neither increases in COX activity nor clinical improvement. The brain levels of copper, noradrenaline, and dopamine in the mice treated on day 12 were the same as those in animals treated on day 4 or 7. The in vitro activities of dopamine-beta-hydroxylase of the brain were also the same among the treated mice, irrespective of the date of treatment. The results indicate that delays in copper treatment produce irreversible changes in COX activity of the brain and lead to clinical unresponsiveness to treatment.
对半合子斑驳花斑小鼠（Mobr/y小鼠）进行皮下注射铜处理，并在出生后第14天断头。在第4天或第7天给予每克10微克铜的小鼠，其脑线粒体细胞色素c氧化酶（COX）活性与未处理的Mobr/y动物相比显著增加，且这些小鼠没有神经症状。在第12天给予每克10微克铜的小鼠，COX活性既未增加，临床症状也未改善。第12天接受处理的小鼠脑中铜、去甲肾上腺素和多巴胺的水平与第4天或第7天接受处理的动物相同。无论处理日期如何，处理后的小鼠脑多巴胺-β-羟化酶的体外活性也相同。结果表明，铜处理延迟会导致脑COX活性发生不可逆变化，并导致临床治疗无反应。
