Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in rat striatal tissue slices

Manganese and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are known to induce neurological pathologies similar to that of parkinsonism. Previo us studies performed in rat striatal slices have shown that MPTP and relate d compounds inhibit tyrosine hydroxylation, a rate-limiting step of dopamin e biosynthesis. Here, we reported that manganese inhibited tyrosine hydroxy lation in rat striatal slices. In addition, manganese caused increase in th e levels of lactate indicating that aerobic glycolysis was inhibited in str iatal slices. This inhibition was unique to manganese since other divalent cations, such as magnesium and zinc, did not increase lactate concentration s. These results suggest that the mechanisms by which manganese produces dy sfunction of the nervous system are similar to those of MPTP. (C) 2001 Else vier Science Ireland Ltd. All rights reserved.