Age-dependent dopaminergic dysfunction in Nurr1 knockout mice
Age-dependent dopaminergic dysfunction in Nurr1 knockout mice
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DOI：
10.1016/j.expneurol.2004.08.035
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发表时间：
2005-01-01
影响因子：
5.3
通讯作者：
Le, WD
中科院分区：
文献类型：
--
作者：
Jiang, CT;Wan, XH;Le, WD
Nurr 1基因编码核受体超家族中的转录因子，在中脑多巴胺能系统的发育中起着重要作用。为了研究Nurr 1表达在维持成熟黑质纹状体DA能神经元功能中的年龄依赖性作用，我们检查了运动行为，测定了黑质纹状体多巴胺（DA）水平和黑质DA能神经元的数量，并测量了不同年龄的杂合Nurr 1缺陷（Nurr 1 +/-）和野生型小鼠中几种DA能神经元相关基因的表达。与相同年龄的野生型小鼠相比，老年Nurr 1 +/-小鼠（>15个月）的转棒表现和运动活动均显著降低，表明运动障碍类似于帕金森病缺陷。此外，老年Nurr 1 +/-小鼠的异常运动行为与纹状体中DA水平降低、黑质中DA能神经元数量减少以及黑质中Nurr 1和DA转运蛋白表达减少相关。我们的数据表明，Nurr 1在黑质DA能神经元的功能维持和存活中起着重要作用，并表明Nurr 1 +/-小鼠是研究帕金森病（PD）发病机制和探索疾病改善策略的有用动物模型。(C)2004年爱思唯尔公司All rights reserved.
The Nurr1 gene, which codes for a transcriptional factor in the nuclear receptor superfamily, plays an important role in the development of the mesencephalic dopaminergic (DAergic) system. To study the age-dependent effects of Nurr1 expression in maintaining mature nigrostriatal DAergic neuronal function, we examined motor behaviors, determined nigrostriatal dopamine (DA) levels and the number of nigral DAergic neurons, and measured the expression of several DAergic neuron-associated genes in heterozygous Nurr1-deficient (Nurr1+/-) and wild-type mice of different ages. In contrast to the same-aged, wild-type mice, old Nurr1+/- mice (>15 months) had a significant decrease in both rotarod performance and locomotor activities, suggesting a motor impairment that is analogous to parkinsonian deficit. Furthermore, the abnormal motor behaviors in old Nurr1+/- mice were associated with decreased DA levels in the striatum, decreased number of DAergic neurons in the nigra, and reduced expression of Nurr1 and DA transporter in the nigra. Our data indicate that Nurr1 plays an important role in the functional maintenance and survival of nigral DAergic neurons and suggest that the Nurr1+/- mouse is a useful animal model to study the pathogenesis of Parkinson disease (PD) and to explore disease-modifying strategies. (C) 2004 Elsevier Inc. All rights reserved.