Chlordecone-induced alterations in content and subcellular distribution of calcium in mouse brain.

Abstract

The neurotoxic insecticide chlordecone was administered orally to "young" (4-6 wk old) and "old" (6 mo old) mice in a dose of 25 mg/kg X d in 10 ml/kg corn oil. Age-matched control mice received 10 ml/kg X d corn oil. The acute (24 h after a single dose) and subchronic (24 h after 8 daily doses) effects of chlordecone on content and subcellular distribution of Ca in the brain were studied. Significant differences in Ca content and subcellular distribution were found between the young and old control mice. Whole brains of old mice had significantly greater amounts of total brain Ca, protein-bound Ca, and mitochondrial Ca than did those of young mice, but significantly less nuclear and cytosol Ca. Acute exposure to chlordecone (no signs of neurotoxicity) increased significantly total brain, protein-bound, nuclear, mitochondrial, and myelin Ca in brains from young mice. However, under the same chlordecone exposure conditions, old mice had significantly decreased total brain, protein-bound, and mitochondrial Ca with significantly increased nuclear Ca content. It is suggested that aging caused altered biochemical responses to the neurotoxic agent, at least at subtoxic doses or exposure times. When young mice received chlordecone for 8 d and were suffering severe chlordecone-induced tremors, at the times of sacrifice, their brains were found to have significantly decreased total, protein-bound, myelin, and synaptosomal Ca. Nuclear Ca was increased. The increased excitation of the central nervous system evidenced as severe tremors induced by chlordecone might be due, at least in part, to chlordecone-induced Ca deficiency in brain synaptosomes. Such Ca deficiency may decrease the Ca-dependent release of the CNS inhibitory transmitters gamma-aminobutyric acid (GABA) and dopamine.