title: Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson's disease.
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.
authors.affiliation: Center on Addiction, Learning, Memory, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Lifen
authors.initials: L
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xie
authors.forename: John A
authors.initials: JA
authors.lastname: Dani
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics* / Q000502:physiology; D006580:Genetic Carrier Screening; D051379:Mice; D018345:Mice, Knockout; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D004298:Dopamine