Regulation of dopamine presynaptic markers and receptors in the striatum of DJ-1 and Pink1 knockout rats.
Regulation of dopamine presynaptic markers and receptors in the striatum of DJ-1 and Pink1 knockout rats.
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DOI：
10.1016/j.neulet.2013.10.034
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发表时间：
2013-12-17
影响因子：
2.5
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Sun J;Kouranova E;Cui X;Mach RH;Xu J
DJ-1（Park 7）或PTEN诱导的推定激酶1（Pink 1或PARK 6）基因中的致病性常染色体隐性突变与家族性帕金森病（PD）相关。关于涉及DJ-1和Pink 1突变的病理机制尚不清楚。在这里，我们通过表达谱分析和定量放射自显影来测量转基因大鼠和野生型对照大鼠纹状体中多巴胺D1、D2、D3受体、囊泡单胺转运蛋白2型（VMAT 2）和多巴胺转运蛋白（DAT）的密度，对DJ-1和Pink 1基因敲除大鼠进行了表征。使用已知参与PD的84个基因的市售阵列进行的表达谱分析表明，在每个转基因大鼠模型中，只有靶基因显著下调。分别使用[3 H] SCH 23390、[3 H]二氢丁苯那嗪和[3 H] WIN 35428测量D1受体、VMAT 2和DAT。在两种模型中均未观察到DAT密度的显著变化。Pink 1基因敲除后VMAT 2和D1受体密度无明显变化，而DJ-1基因敲除后VMAT 2和D1受体密度均明显增加。通过放射性配体[3 H]WC-10和[3 H]雷氯必利结合的数学分析确定的D2和D3受体的密度在两种敲除模型中均显著增加。纹状体中多巴胺突触前标记物和受体表达的这些独特变化可能反映了DJ-1与Pink 1基因敲除大鼠家族性PD模型中多巴胺系统的不同代偿调节。
Pathogenic autosomal recessive mutations in the DJ-1 (Park7) or the PTEN-induced putative kinase 1 (Pink1 or PARK6) genes are associated with familial Parkinson’s disease (PD). It is not well known regarding the pathological mechanisms involving the DJ-1 and Pink1 mutations. Here we characterized DJ-1 and Pink1 knockout rats both through expression profiling and using quantitative autoradiography to measure the densities of the dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2) and dopamine transporter (DAT) in the striatum of transgenic rats and wild type controls. Expression profiling with a commercially available array of 84 genes known to be involved in PD indicated that only the target gene was significantly downregulated in each transgenic rat model. D1 receptor, VMAT2, and DAT were measured using [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]WIN35428, respectively. No significant changes were observed in the density of DAT in either model. Although the densities of VMAT2 and D1 receptor were unchanged in Pink1 knockout, but both were increased in DJ-1 knockout rats. The densities of D2 and D3 receptors, determined by mathematical analysis of binding of radioligands [3H]WC-10 and [3H]raclopride, were significantly increased in both knockout models. These distinctive changes in the expression of dopamine presynaptic markers and receptors in the striatum may reflect different compensatory regulation of dopamine system in DJ-1 versus Pink1 knockout rat models of familial PD.
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影响因子：
3.3
作者：
Dekker, MCJ;Eshuis, SA;Leenders, KL
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