Neurotoxicity of MPTP and MPP+ in vitro: characterization using specific cell lines

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its putative toxic metabolite 1-methyl-4-phenylpyridinium ion MPP+ were studied with specific neuronal and glial cell lines in vitro. MPTP had no morphological effect on actively growing neuroblastoma N2AB-1 cells or C6 glioma cells nor did it affect cell numbers. However, a low dose of MPP+ (33.7 microM) was cytotoxic to mitotic N2AB-1 cells inducing vacuole formation, cell lysis, and inhibiting cell growth over a 3-day period. Protein synthesis was inhibited in a dose-dependent fashion in MPP+ treated N2AB-1 cells after 24 h exposure while 33.7 microM of this toxin induced a 50% decrease in protein synthesis as early as 5 h after treatment of these cells. Differentiated, neurite-bearing N2AB-1 cells exhibited a loss of neurites and a change in cell size and shape following exposure to 0.33, 3.37 and 33.7 microM MPP+ after 24 h and some cells appeared to be mitogenically stimulated indicating MPP+ may act as a teratogen. C6 glioma cells, however, were resistant to MPP+. While mitotic N2AB-1 cells incubated with MPTP produced only traces of MPP+, C6 glioma cells generated significant amounts of this metabolite (3.6 microM). Moreover, although the morphology and cell number of cocultures did not change in the presence of MPTP, glioma-neuroblastoma cocultures produced 2.90 microM MPP+ which decreased protein synthesis by 18%.(ABSTRACT TRUNCATED AT 250 WORDS)