6-HYDROXYDOPAMINE-MEDIATED INDUCTION OF RAT-BRAIN METALLOTHIONEIN-I MESSENGER-RNA

Oxidative stress, resulting either from excess generation or reduced s cavenging of free radicals, has been proposed to play a role in damagi ng striatal neurons in Parkinson's disease. Since metallothionein is a ble to regulate the intracellular redox potential, we have undertaken a group of experiments to learn whether or not 6-hydroxydopamine, whic h generates free radicals and is toxic to dopaminergic neurons, could alter the levels of zinc and metallothionein in the brain. The lesioni ng of the rat striatum with 6-hydroxydopamine (8.0 mu g in 4 mu I 0.02 % ascorbic acid) resulted in a reduction in the levels of zinc and met allothionein in the striatum but nor other brain regions tested. Howev er, the intracerebroventricular administration of 6-hydroxydopamine, i n a dosage regimen that does not lesion catecholaminergic pathways bur causes oxidative stress, enhanced dramatically the level of metalloth ionein I mRNA in some brain areas such as hippocampus, arcuate nucleus , choroid plexus, and granular layer of cerebellum, but not in the cau date putamen. The results of these studies are interpreted to suggest that zinc or metallothionein are altered in conditions where oxidative stress has ta ken place. Moreover, it is proposed that areas of brain , such as striatum containing high concentrations of iron, but low lev els of inducible metallothionein are particularly vulnerable to oxidat ive stress. (C) 1996 Intox Press, Inc.