NEUROTOXIC EFFECTS OF MERCURY - REVIEW

The significant literature concerning the neurotoxic effects of Hg, biochemical, physiological and morphological, is reviewed. Hg was found to penetrate and damage the blood-brain barrier very rapidly, leading to a dysfunction of the blood-brain barrier system. Both biochemical and EM histochemical analysis revealed that, intracellularly, Hg was bound to the membranous organelles such as mitochondria, endoplasmic reticulum, Golgi complex, nuclear envelopes and lysosomes. Only very minimal amounts of Hg were found within the nucleus. Biochemical and cytochemical studies also indicated that drastic reduction of neuronal RNA and protein synthesis occurred in Hg-intoxicated animals. Reduction of the protein synthesis was believed to lead to eventual cell death in these neurons. A regain in the neuron RNA level was also observed in prolonged intoxication with mercuric bichloride. Such an observation could also be correlated with the increasing tolerance to Hg toxicity by these animals. Disturbance of the enzymatic systems in the glycolytic pathway in the brain was also reported in Hg-poisoned animals. Neurophysiological study demonstrated abnormal excitation spikes in the Hg-intoxicated neurons. The suggestion that neuronal cell body injury preceded axonal injury was made. The large-caliber myelinated fibers probably were more vulnerable than the smaller nerve fibers to Hg toxicity. Pathological findings on Minamata disease [Japan] were summarized. In experimental models, the sensory neurons in the spinal ganglia and granule cells in the cerebellum were most vulnerable to Hg poisoning. Ultrastructural studies indicated that vacuolar degeneration of the neurons was mainly associated with inorganic Hg intoxication, while coagulative type of degeneration was found mostly in organic Hg poisoning. Degenerative changes in the nerve fibers were also observed. Based on the biochemical, physiological and pathological findings on Hg intoxication, a working hypothesis on the pathogenetic mechanism of Hg on the nervous system is proposed.