Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra
Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra
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DOI：
10.1002/cne.10261
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发表时间：
2002-08-26
影响因子：
2.5
通讯作者：
Kordower, JH
中科院分区：
文献类型：
--
作者：
Chu, YP;Kompoliti, K;Kordower, JH
核受体相关因子1(Nurr1)是核受体超家族的一员，与发育和成熟的中脑神经元中多巴胺能(DA)表型的诱导有关。众所周知，多巴胺能黑质纹状体功能随年龄增长而下降。年龄相关的DA表型标记缺陷是否与Nurr1表达的改变相关尚不清楚。本研究发现，几乎所有的酪氨酸羟基酶免疫反应(TH-ir)神经元在青年人黑质都是Nurr1免疫反应阳性(Nurr1-ir)。体视学计数显示，与青年组相比，中年组(23.13%)和老年组(46.33%)的Nurr1-ir黑质神经元数量明显减少。Nurr1-ir神经元的丢失与TH-ir神经元数量的减少类似。在这方面，中老年人(11.10%)和老年人(45.97%)的TH阳性神经元数量减少，并且这种缺失与Nurr1阳性神经元的缺失高度相关(r=0.92)。相比之下，含黑色素的黑质神经元的数量在不同年龄组之间总体上是稳定的，这表明Nurr1和TH的变化反映了与年龄相关的表型变化，而不是坦率的神经元退化。为了支持这一概念，对Nurr1-ir和TH-ir荧光强度的共聚焦显微镜分析显示，Nurr1和TH免疫荧光随着年龄的增加而平行减少。这些数据表明，与年龄相关的DA表型标记物的下降与SN中Nurr1表达的下调有关。(C)2002年Wiley-Liss，Inc.
Nuclear receptor-related factor 1 (Nurr1), a member of the nuclear receptor superfamily, is associated with the induction of dopaminergic (DA) phenotypes in developing and mature midbrain neurons. It is well established that dopaminergic nigrostriatal function decreases with age. Whether age-related deficits in DA phenotypic markers are associated with alterations in Nurr1 expression is unknown. The present study found that virtually all of tyrosine hydroxylase-immunoreactive (TH-ir) neurons within the young adult human substantia nigra were Nurr1-immunoreactive (Nurr1-ir) positive. Stereologic counts revealed a significant reduction in the number of Nurr1-ir nigral neurons in middle-aged (23.13%) and aged (46.33%) individuals relative to young subjects. The loss of Nurr1-ir neurons was associated with a similar decline in TH-ir neuron number. In this regard, TH-ir neuronal number was decreased in middle-aged (11.10%) and in aged (45.97%) subjects, and this loss of TH-ir neurons was highly correlated (r = 0.92) with the loss of Nurr1-ir neurons. In contrast, the number of melanin-containing nigral neuron number was generally stable across age groups, indicating that changes in Nurr1 and TH reflect phenotypic age-related changes and not frank neuronal degeneration. In support of this concept, confocal microscopic analyses of Nurr1-ir and TH-ir fluorescence intensity revealed parallel decreases in Nurr1- and TH-immunofluorescence as a function of age. These data demonstrate that age-related decline of DA phenotypic markers is associated with down-regulation of Nurr1 expression in the SN. (C) 2002 Wiley-Liss, Inc.