Neurotoxic effects of mercury--a review.

Abstract The significant literature concerning the neurotoxic effects of mercury, biochemical, physiological, and morphological, is reviewed. Mercury 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 electron-microscopic histochemical analysis revealed that, intracellularly, mercury was bound to the membranous organelles such as mitochondria, endoplasmic reticulum, Golgi complex, nuclear envelopes and lysosomes. Only very minimal amounts of mercury were found within the nucleus. Biochemical and cytochemical studies also indicated that drastic reduction of neuronal RNA and protein synthesis occurred in mercury-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 mercury toxicity by these animals. Disturbance of the enzymatic systems in the glycolytic pathway in the brain was also reported in mercury-poisoned animals. Neurophysiological study demonstrated abnormal excitation spikes in the mercury-intoxicated neurons. The suggestion that neuronal cell body injury preceded axonal injury was made. It was also suggested that the large-caliber myelinated fibers were more vulnerable than the smaller nerve fibers to mercury toxicity. Pathological findings on Minamata disease were summarized. In experimental models, it was found that the sensory neurons in the spinal ganglia and granule cells in the cerebellum were most vulnerable to mercury poisoning. Ultrastructural studies indicated that vacuolar degeneration of the neurons was mainly associated with inorganic mercury intoxication, while coagulative type of degeneration was found mostly in organic mercury poisoning. Degenerative changes in the nerve fibers were also observed. Based on the biochemical, physiological, and pathological findings on mercury intoxication, a working hypothesis on the pathogenetic mechanism of mercury on the nervous system is proposed.