Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 5, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.03.022
Keywords
Dopamine reuptake; Striatum; Parkinsonian; Animal model; Age-dependent; Voltammetry
Categories
Funding
- National Institutes of Health [NINDS NS21229, NIDA DA09411]
- Diana Helis Henry Medical Research Foundation
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The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knockout (Nurr1 +/-) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/-) mice: 3-6, 9-12, and 15-23 mo old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/- mice (3-6 mo) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/- mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/- mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. (C) 2012 Elsevier Inc. All rights reserved.
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