Reduced Nurr1 expression increases the vulnerability of mesencephalic dopamine neurons to MPTP-induced injury

Weidong Le, Orla M. Conneely, Y. He, Joseph Jankovic, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Mutation in the Nurr1 gene, a member of the nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in the midbrain of null mice. Homozygous Nurr1 knockout mice (Nurr1-/-) die 1 day after birth, but heterozygous mice (Nurr1+/-) survive postnatally without obvious locomotor deficits. Although adult Nurr1+/- mice show significantly reduced Nurr1 protein levels in the substantia nigra (SN), they display a normal range of tyrosine hydroxylase-positive neuron numbers in the SN and normal levels of dopamine in the striatum. The reduction in Nurr1 expression in Nurr1+/- mice, however, confers increased vulnerability to the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) compared with wild-type (Nurr1+/+) mice. This study suggests that Nurr1 may play an important role in maintaining mature mesencephalic dopaminergic neuron function and that a defect in Nurr1 may increase susceptibility to SN injury.

Original languageEnglish (US)
Pages (from-to)2218-2221
Number of pages4
JournalJournal of Neurochemistry
Volume73
Issue number5
DOIs
StatePublished - 1999

Keywords

  • 1-Methyl-4- phenyl-1,2,3,6-tetrahydropyridine
  • Dopaminergic neurons
  • Knockout mice
  • Mesencephalon
  • Nurr1
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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