1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons

Juan Sanchez-Ramos, John N. Barrett, Menek Goldstein, William J. Weiner, Franz Hefti

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Dopaminergic neurons were studied in cultures of dissociated cells from the ventral mesencephalon of fetal rat embryos (gestational day E15-16). After a week of growth, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) was added to the growth medium for 24 h. Dopaminergic neurons were then visualized with tyrosine hydroxylase (TH) immunocytochemistry or catecholamine (CA) cytofluorescence. Concentrations of MPTP in the range of 10 to 100 μM obliterated CA fluorescence without affecting the number of TH-positive neurons. At concentrations greater than 100 μM, MPTP decreased the number of TH-positive neurons as well as the number of all other cell types. MPP+ (0.1-10.0 μM) produced a decrease in the number of TH-positive neurons without decreasing the total number of all cell types. The findings indicate that MPP+ but not MPTP is able to selectively destroy rat dopaminergic neurons in our cultures. The selective toxicity of MPP+ for dopaminergic neurons was partially prevented by pretreatment and co-incubation with mazindol (a selective inhibitor of dopamine uptake) but not by desipramine or deprenil, in confirmation of the notion that MPP+ enters dopaminergic neurons by the specific uptake mechanism for dopamine.

Original languageEnglish (US)
Pages (from-to)215-220
Number of pages6
JournalNeuroscience Letters
Volume72
Issue number2
DOIs
StatePublished - Dec 12 1986

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  • 1-Methyl-4-phenylpyridinium (MPP)
  • Cell culture
  • Dopaminergic neuron
  • Parkinson's disease
  • Substantia nigra
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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