Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP

Manjit K. Sanghera, Kebreten Manaye, Anne McMahon, Patricia K. Sonsalla, Dwight C. German

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

THE neurotoxin MPTP kills only certain midbrain dopaminergic (DA) neurons to produce a model of Parkinson's disease. The dopamine transporter (DAT) is important to MPTP toxicity because to be neurotoxic, an MPTP metabolite must first gain access to the DA neuron via the DAT. Also, MPTP is less toxic to DA neurons that contain the putative neuroprotective calcium- binding protein calbindin-D(28k) (CB). The present study examined the relative importance of DAT activity and CB for cellular vulnerability to MPTP-induced degeneration in the C57BL/6 mouse. Cells that were vulnerable to MPTP were found to contain high levels of DAT mRNA, whereas cells that were not vulnerable contained low levels. Also, the few substantia nigra cells remaining after a toxic dose of MPTP contained only low levels of DAT mRNA. However, there was not a strong relationship between cellular resistance to MPTP toxicity and cells containing CB. These data provide in vivo evidence for a direct correlation between midbrain cellular vulnerability to MPTP toxicity and the activity of the DAT.

Original languageEnglish (US)
Pages (from-to)3327-3331
Number of pages5
JournalNeuroReport
Volume8
Issue number15
DOIs
StatePublished - Jan 1 1997

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  • Calbindin-D(28k) (CB)
  • Dopamine transporter (DAT)
  • Immunocytochemistry
  • In situ hybridization
  • Mice
  • Midbrain dopaminergic (DA) neurons

ASJC Scopus subject areas

  • Neuroscience(all)

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