TY - JOUR
T1 - Reduced Nurr1 expression increases the vulnerability of mesencephalic dopamine neurons to MPTP-induced injury
AU - Le, Weidong
AU - Conneely, Orla M.
AU - He, Y.
AU - Jankovic, Joseph
AU - Appel, Stanley H.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - 1-Methyl-4- phenyl-1,2,3,6-tetrahydropyridine
KW - Dopaminergic neurons
KW - Knockout mice
KW - Mesencephalon
KW - Nurr1
KW - Parkinson's disease
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U2 - 10.1046/j.1471-4159.1999.02218.x
DO - 10.1046/j.1471-4159.1999.02218.x
M3 - Article
C2 - 10537083
AN - SCOPUS:0032692692
SN - 0022-3042
VL - 73
SP - 2218
EP - 2221
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -