THE DEPOSITION OF EXOGENOUS COPPER UNDER EXPERIMENTAL CONDITIONS WITH OBSERVATIONS ON ITS NEUROTOXIC AND NEPHROTOXIC...

Goldfish kept in water containing ionized copper and a detergent added with the aim of decreasing coagulation of the mucus on the gills, took in and retained this metal in their brains, livers, and kidneys, in concentrations comparable to those that occur naturally in Wilson's disease, as chemical assays disclosed. Histochemical studies made it clear that much copper had accumulated within the large neurons, principally in those of the telencephalon and anterior horn region of the spinal cord and in the tubular epithelial cells of the kidneys, the nuclei of the parenchymal cells of the liver, the sarcoplasm of the skeletal muscle, and in the epithelial covering of the gills. The intraneuronal deposition of copper was regularly associated after a time with conspicuous cytologic changes, notably contraction and hyperchromaticity of the nerve cells with tortuosity and fragmentation of the axis cylinders and lysis and loss of neurons. The accumulation of metal in the renal epithelium was frequently accompanied by necrosis and was regularly associated with hyperplasia and calcification of the epithelial cells of the larger renal tubules in all goldfish kept for prolonged periods in copper-rich water. The deposition of copper in the liver was not accompanied by consistent cytologic changes. The similarity of the cytologic alterations induced in the central nervous systems by copper and those that occur naturally in hepatolenticular degeneration in human beings provides evidence that copper itself plays an important role in the pathologic alterations of the brain in Wilson's disease.