Prohaska J R, Smith T L
J Nutr. 1982 Sep;112(9):1706-17. doi: 10.1093/jn/112.9.1706.
Previous studies by others indicated that alterations in brain catecholamines were different for perinatal copper deficiency produced by diet in rats and that resulting from a genetic mutation of the X-chromosome, Menkes' syndrome in humans and brindled mice. Thus, copper deficiency was studied in a model in which dietary and genetic deficiency (brindled mice) were compared in two strains of the same species. C57BL and C3H/HeJ mice. Dietary copper deficiency was also produced in rats for comparison. In brain, both dietary and genetic copper deficiency resulted in impaired growth, low brain copper levels, greatly decreased norepinephrine concentrations but normal dopamine levels. The activity of brain cytochrome oxidase was greatly depressed following both dietary and genetic copper deficiency, suggesting a functional deficit of copper. However, the activity of another cuproenzyme, dopamine-beta-hydroxylase, was significantly elevated in deficient animals. The elevation was observed when either copper or N-ethylmaleimide was added to inactivate an endogenous inhibitor. The cause of low brain norepinephrine remains unknown; however, depressed brain norepinephrine may be partly responsible for functional changes in the deficient animals, such as hypomyelination, since the activity of the myelin protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, was lower in the most deficient animals.
其他人之前的研究表明，饮食导致的大鼠围产期铜缺乏与X染色体基因突变（人类的门克斯综合征和花斑小鼠）所导致的脑儿茶酚胺变化不同。因此，在一个模型中对铜缺乏进行了研究，该模型比较了同一物种两个品系（C57BL和C3H/HeJ小鼠）的饮食性铜缺乏和遗传性铜缺乏（花斑小鼠）。还在大鼠中制造了饮食性铜缺乏以作比较。在脑中，饮食性和遗传性铜缺乏均导致生长受损、脑铜水平降低、去甲肾上腺素浓度大幅下降但多巴胺水平正常。饮食性和遗传性铜缺乏后，脑细胞色素氧化酶的活性均大幅降低，表明铜存在功能缺陷。然而，在缺乏铜的动物中，另一种铜酶——多巴胺-β-羟化酶的活性显著升高。当添加铜或N-乙基马来酰亚胺以灭活内源性抑制剂时，观察到了这种升高。脑去甲肾上腺素水平低的原因尚不清楚；然而，脑去甲肾上腺素水平降低可能部分导致了缺乏铜的动物的功能变化，如髓鞘形成不足，因为在最缺乏铜的动物中，髓鞘蛋白2',3'-环核苷酸3'-磷酸二酯酶的活性较低。
