[An electron microscopic study of the cerebrum in experimental copper loading (author's transl)]

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.