TY - JOUR
T1 - Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson's disease.
AU - Zhang, Lifen
AU - Le, Weidong
AU - Xie, Wenjie
AU - Dani, John A.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health: NINDS NS21229 and NIDA DA09411 . This study also was supported by the Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine. The first two authors contributed equally.
Copyright:
MEDLINE® is the source for the citation and abstract of this record.
PY - 2012/5
Y1 - 2012/5
N2 - 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 Â
AB - 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 Â
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M3 - Article
C2 - 21531044
AN - SCOPUS:84858342244
SN - 0197-4580
VL - 33
SP - 1001.e7-16
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 5
ER -