Effects of gender on nigral gene expression and parkinson disease
Effects of gender on nigral gene expression and parkinson disease
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DOI：
10.1016/j.nbd.2007.02.009
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发表时间：
2007-06-01
影响因子：
6.1
通讯作者：
Standaert, David G.
中科院分区：
文献类型：
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作者：
Cantuti-Castelvetri, Ippolita;Keller-McGandy, Christine;Standaert, David G.
为了鉴定男性和女性对照和帕金森病（PD）患者的黑质腹侧部（SNc）中人类多巴胺（DA）神经元的基因表达模式，我们使用激光捕获显微切割和微阵列从16名受试者（4名男性PD，4名女性PD，4名男性和4名女性对照）的冷冻SNc中收获DA神经元。我们评估了具有超几何分布的功能类别的富集。我们观察到性别对DA神经元基因表达的影响是普遍的。相对于男性，女性中上调的基因主要涉及信号转导和神经元成熟，而在男性中，一些上调的基因（α-突触核蛋白和PINK）先前与PD的发病机制有关。在女性PD患者中，我们发现蛋白激酶活性基因、蛋白水解基因和WNT信号通路基因发生改变，而在男性PD患者中，蛋白结合蛋白和铜结合蛋白发生改变，我们的数据揭示了人类黑质多巴胺能神经元基因表达的广泛性别差异，这可能是男性PD易感性的基础。此外，我们表明，性别影响对PD的反应，这表明疾病的性质和对治疗的反应可能是性别依赖性的。(c)2007爱思唯尔公司All rights reserved.
To identify gene expression patterns in human dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of male and female control and Parkinson disease (PD) patients, we harvested DA neurons from frozen SNc from 16 subjects (4 male PDs, 4 female PDs, 4 male and 4 female controls) using Laser Capture microdissection and microarrays. We assessed for enrichment of functional categories with a hypergeometric distribution. The data were validated with QPCR.We observed that gender has a pervasive effect on gene expression in DA neurons. Genes upregulated in females relative to males are mainly involved in signal transduction and neuronal maturation, while in males some of the upregulated genes (alpha-synuclein and PINK]) were previously implicated in the pathogenesis of PD. In females with PD we found alterations in genes with protein kinase activity, genes involved in proteolysis and WNT signaling pathway, while in males with PD there were alterations in protein-binding proteins and copper-binding proteins.Our data reveal broad gender-based differences in gene expression in human dopaminergic neurons of SNc that may underlie the predisposition of males to PD. Moreover, we show that gender influences the response to PD, suggesting that the nature of the disease and the response to treatment may be gender-dependent. (c) 2007 Elsevier Inc. All rights reserved.