Serotonin and dopamine striatal innervation in Parkinson's disease and Huntington's chorea
Serotonin and dopamine striatal innervation in Parkinson's disease and Huntington's chorea
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DOI：
10.1016/j.parkreldis.2011.05.012
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发表时间：
2011-09-01
影响因子：
4.1
通讯作者：
Parent, Martin
中科院分区：
文献类型：
--
作者：
Bedard, Catherine;Wallman, Marie-Josee;Parent, Martin
与我们对多巴胺（DA）系统的广泛了解相比，我们对5-羟色胺（5-HT）在影响基底神经节的神经退行性疾病中的作用知之甚少。因此，我们设计了一项研究，旨在描述帕金森病（PD）或亨廷顿病（HD）患者纹状体DA和5-羟色胺系统的状态，并与年龄匹配的对照组进行比较。酪氨酸羟化酶（TH）抗体和5-HT转运蛋白（SERT）抗体分别作为DA和5-HT轴突谱的标记。TH+和SERT +神经支配的密度和模式通过光学密度测量以及标记轴突变异的直接立体学估计来确定。结果显示，PD和HD患者纹状体中TH免疫反应性和TH +轴突终末显著降低，而与对照组相比，PD和HD患者纹状体中SERT免疫染色强度和SERT +轴突变异密度略有增加。这些结果表明，与纹状体5-HT神经支配相比，PD和HD患者的黑质纹状体DA系统明显受损，纹状体5-HT神经支配在这两种情况下略有增加。在PD中观察到的纹状体5-HT增加可能是一种旨在补偿DA去神经支配的神经机制的结果，而纹状体的显著萎缩可能解释了HD中注意到的5-HT神经支配的增加。这些发现强调了DA和5-羟色胺纹状体传入之间复杂的相互作用在适当运动行为的阐述中的重要性。(C) 2011 Elsevier Ltd.版权所有。
In contrast to our vast knowledge of the dopamine (DA) system, much less is known about the involvement of serotonin (5-HT) in neurodegenerative diseases affecting the basal ganglia. Therefore, we designed a study that aimed at characterizing the status of the striatal DA and 5-HT systems in patients who suffered from either Parkinson's (PD) or Huntington's disease (HD), compared to age-matched controls. Antibodies against tyrosine hydroxylase (TH) and 5-HT transporter (SERT) were used as markers of DA and 5-HT axonal profiles, respectively. The density and pattern of TH+ and SERT + innervation were determined by optical density measurements as well as by direct stereological estimates of labeled axon varicosities. The results reveal a significant decrease in TH immunoreactivity and TH + axon terminals throughout the striatum in both PD and HD, whereas the intensity of SERT immunostaining and the density of SERT + axon varicosities were found to be slightly increased in the striatum of PD and HD patients compared to controls. These findings reveal that the nigrostriatal DA system is significantly impaired in both PD and HD compared to the striatal 5-HT innervation, which is slightly increased in these two conditions. The striatal 5-HT augmentation observed in PD might be the result of a neural mechanism designed to compensate for DA denervation, whereas the marked atrophy of the striatum might explain the increase in the 5-HT innervation noted in HD. These findings underline the importance of the complex interplay between DA and 5-HT striatal afferents in the elaboration of appropriate motor behaviour. (C) 2011 Elsevier Ltd. All rights reserved.