Cyclosporin A, an immune suppressor, enhanced neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice

Abstract

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was systemically administrated into C57BL/6N mice for 8 days. Tyrosine hydroxylase activity and dopamine content in striatum and hypothalamus were reduced markedly, and the reduction was more manifest in the striatum. Cyclosporin A, an immune suppresser, enhanced the neurotoxicity of MPTP, when it was injected to mice in combination with MPTP. Tyrosine hydroxylase activity in the striatum was reduced to 109 ± 20 from 350 ± 46 pmol/min/mg protein of control, when mice were injected by MPTP alone. The enzyme activity was further reduced to 68.4 ± 12.2 pmol/min/mg protein by injection of MPTP in combination to cyclosporin A. In addition, dopamine and biopterin contents in the striatum decreased quite in parallel to the reduction of tyrosine hydroxylase activity. On the other hand, cyclosporin A itself did not effect tyrosine hydroxylase activity and dopamine and biopterin contents in the striatum and hypothalamus. These data suggest cumulative effect of cyclosporin A to the neurotoxicity of MPTP.