1. Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson's disease
- Author
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Zhang, Lifen, Le, Weidong, Xie, Wenjie, and Dani, John A.
- Subjects
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DOPAMINERGIC neurons , *CELLULAR signal transduction , *NUCLEAR receptors (Biochemistry) , *PROTEIN deficiency , *PARKINSON'S disease , *AGE factors in disease , *NEURAL development , *TRANSCRIPTION factors , *LABORATORY mice - Abstract
Abstract: 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. [Copyright &y& Elsevier]
- Published
- 2012
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