Neurochemical characterization of dopaminergic neurons in human striatum

Neurochemical characterization of dopaminergic neurons in human striatum
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DOI:
10.1016/j.parkreldis.2005.02.008
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发表时间:
2005-08-01
影响因子:
4.1
通讯作者:
Parent, A
Parent, A
中科院分区:
医学2区
文献类型:
--
作者:
Cossette, M;Lévesque, D;Parent, A

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我们研究了表达酪氨酸羟基酶(TH)mRNA的纹状体神经元的神经化学表型,以确定它们是否在人类纹状体中形成了一类不同的神经元。采用双重原位杂交(ISH)和免疫组织化学(LHC)方法检测TH mRNA阳性的纹状体神经元是否表达成熟神经元(MAP2和Neun)、多巴胺能神经元(DAT和Nurr1)或未成熟神经元(TuJ1)的分子标志物。所有TH基因标记的神经元均表达Neun、DAT和Nurr1,其中约80%的神经元表达MAP2,证实了其神经元和多巴胺能性质。只有约30%的TH基因标记的神经元表达TuJ1,这表明这个异位的多巴胺能神经元主要由成熟神经元组成。然后使用相同的双重ISH/IHC方法来了解这些多巴胺神经元是否显示了成熟的纹状体投射神经元(GAD65和Calbindin)或局部环路神经元(GAD65、Calretinin、生长抑素和小白蛋白)的标记。几乎所有TH标记的神经元都表达GAD65mRNA,其中约30%的神经元表达Calretinin,但没有其他纹状体神经元标记物染色。这些结果表明,大多数人纹状体固有的TH阳性神经元属于纹状体中间神经元的一个独特的亚群,其特征是能够产生多巴胺和GABA。(C)2005爱思唯尔有限公司。保留所有权利。
We examined the neurochemical phenotype of striatal neurons expressing tyrosine hydroxylase (TH) mRNA to determine if they form a distinct class of neurons within the human striatum. Double in situ hybridization (ISH) and immunohistochemical (lHC) procedures were used to know if TH mRNA-positive striatal neurons express molecular markers of mature neurons (MAP2 and NeuN), dopaminergic neurons (DAT and Nurr1) or immature neurons (TuJ1). All TH mRNA-labeled neurons were found to express NeuN, DAT and Nurr1, whereas about 80% of them exhibited MAP2, confirming their neuronal and dopaminergic nature. Only about 30% of TH mRNA-labeled neurons expressed TuJ1, suggesting that this ectopic dopaminergic neuronal population is principally composed of mature neurons. The same double ISH/IHC approach was then used to know if these dopamine neurons display markers of well-established classes of striatal projection neurons (GAD65 and calbindin) or local circuit neurons (GAD65, calretinin, somatostatin and parvalbumin). Virtually all TH-labeled neurons expressed GAD65 mRNA, about 30% of them exhibited calretinin, but none stained for the other striatal neuron markers. These results suggest that the majority of TH-positive neurons intrinsic to the human striatum belong to a distinct subpopulation of striatal interneurons characterized by their ability to produce dopamine and GABA. (C) 2005 Elsevier Ltd. All rights reserved.