strychnine and Manganese-Poisoning

Manganese (Mn) poisoning is characterized by central nervous system manifestations, including psychiatric disturbances and extrapyramidal disorders. This metal is thought to produce neuronal degeneration due to cytotoxic products originated by oxidative stress and through an indirect excitotoxic process. In previous studies, we have found a reduction in the density of N-methyl-D-aspartate (NMDA) recognition sites in some brain areas of Mn-treated mice. Due to the close relationship between NMDA sites and strychnine-insensitive glycine (Gly) modulatory sites in the NMDA receptor complex, the [3H]-glycine ([3H]-Gly) binding was analyzed by autoradiographic methods in the brain of mice treated with manganese chloride for 8 weeks. Among all analyzed areas, only the globus pallidus showed a significant reduction in [3H]-Gly binding (27-28%). The Gly binding decrease, focalized in the globus pallidus, could reflect a degeneration of structures containing strychnine-insensitive Gly receptors, since this area is the most frequently reported damaged brain region in Mn intoxication. However, it might also be due to a Gly receptor down-regulation to control NMDA complex activation during Mn poisoning.

Topics: Animals; Globus Pallidus; Male; Manganese; Manganese Poisoning; Mice; Receptors, Glycine; Receptors, N-Methyl-D-Aspartate; Strychnine

Manganese neurotoxicity has been recognized among industrial workers as a consequence of chronic exposure to the metal in the form of fumes or dust. Hazards for the general population, including newborn and developing children, and other living organisms may also originate from prolonged low-level exposure to manganese and its organometallic compounds released into the environment as a result of their variety of applications. Experimental evidence has been presented to show that developing mice and rats are not able to excrete manganese for first 17-18 days of life, with excessive tissue accumulation, and their brain is more susceptible to the neurotoxic effects of manganese. Prolonged exposure to manganese causes depletion of dopamine and other monoamines in adult rats. The short-term exposure produces an increase in the binding of dopaminergic antagonist [3H]-spiroperidol to striatal membranes without affecting the other neurotransmitter receptors at low doses (10 mg/kg X 15). A higher dose (15 mg/kg X 15), causes a decrease in cerebral GABA, frontal cortical serotonin and striatal muscarinic binding and an increase in binding of [3H]-spiroperidol to striatal membranes. No significant changes occur in the levels of dopamine or serotonin at either of these two doses. The neonatal rat in certain respects shows a different effect on dopamine levels and receptor sensitivity. Exposure to manganese causes an increase in levels of dopamine and norepinephrine. Neonatal exposure to manganese (10 mg/kg X 15) produces a decrease in binding of [3H]-spiroperidol to striatal membranes and of serotonin to frontal cortical membranes.

Topics: Aging; Animals; Animals, Newborn; Biogenic Amines; Cerebellum; Haplorhini; Manganese Poisoning; Muscimol; Neurotransmitter Agents; Quinuclidinyl Benzilate; Rabbits; Rats; Receptors, Dopamine; Receptors, Neurotransmitter; Receptors, Serotonin; Spiperone; Strychnine