Muraoka S
Hokkaido Igaku Zasshi. 1980 Nov;55(6):557-74.
An electron microscopic study was performed to elucidate the ultrastructural alterations of the cerebrum in experimental copper loading. Copper acetate solution was administered intravenously to nine adult dogs in a dose of 1.5 mg free copper per kilogram of body weight every other day for 13 to 112 days. Eight adult dogs were used for control. Tissue for ultrastructural examination and determination of copper concentration was taken from the cerebral cortex, cerebral medulla, caudate nucleus, and thalamus. The copper concentration was determined by atomic absorption spectrophotometry. 1) Copper Concentration of the Cerebrum Mean copper concentration in each part of the brain of the copper loaded dogs increased about two-fold of each mean value of the control group. No significant correlation was observed between copper concentration and the total dosage or duration of administration. 2) Ultrastructural Findings It was noteworthy that many osmiophilic concentric lamellar structures (or myelin figures) were observed in nerve cells, especially neuronal processes-both axons and dendrites, rather than in glial cells. The same structures were found within mitochondria in endothelial cells of capillaries and arterioles. Vascular feet of astrocytes abutting these capillaries displayed marked edematous swelling. From these findings, I considered the following possibility; 1) These lamellar structures in nerve cells were thought to be autophagic vacuoles and residual bodies derived from disintegrated organelles especially mitochondria digested by lysosomal enzymes in autophagic process. As many of them were found in nerve cells rather than in glial cells, I considered that copper is more toxic to nerve cells than to glial cells. 2) The same structures were found within mitochondria in endothelial cells of capillaries and arterioles. In their formation, it was assumed that lysosomal enzymes were not concerned. As copper is a divalent metal and is known to be an ATPase inhibitor, I speculate that copper nonenergizes mitochondria and then cristae fuse and roll into scroll. These become denser and consequently intramitochondrial lamellar structures are formed. These alterations of mitochondria are thought to influence the permeability of the blood-brain barrier.
进行了一项电子显微镜研究，以阐明实验性铜负荷时大脑的超微结构改变。每隔一天给9只成年犬静脉注射醋酸铜溶液，剂量为每千克体重1.5毫克游离铜，持续13至112天。8只成年犬用作对照。从大脑皮层、脑髓质、尾状核和丘脑获取用于超微结构检查和铜浓度测定的组织。通过原子吸收分光光度法测定铜浓度。1）大脑的铜浓度 铜负荷犬大脑各部位的平均铜浓度增加到对照组各平均值的约两倍。未观察到铜浓度与总给药剂量或给药持续时间之间存在显著相关性。2）超微结构发现 值得注意的是，在神经细胞中观察到许多嗜锇性同心层状结构（或髓鞘样结构），特别是在神经突起——轴突和树突中，而不是在神经胶质细胞中。在毛细血管和小动脉内皮细胞的线粒体内也发现了相同的结构。与这些毛细血管相邻的星形胶质细胞的血管足显示出明显的水肿肿胀。基于这些发现，我考虑了以下可能性：1）神经细胞中的这些层状结构被认为是自噬泡和残余体，源自自噬过程中被溶酶体酶消化的解体细胞器，尤其是线粒体。由于在神经细胞中发现的此类结构比在神经胶质细胞中更多，我认为铜对神经细胞的毒性比对神经胶质细胞更大。2）在毛细血管和小动脉内皮细胞的线粒体内也发现了相同的结构。在其形成过程中，假定溶酶体酶不参与。由于铜是一种二价金属，并且已知是一种ATP酶抑制剂，我推测铜使线粒体失去能量，然后嵴融合并卷成卷轴状。这些变得更致密，因此形成线粒体内层状结构。线粒体的这些改变被认为会影响血脑屏障的通透性。
