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首页> 外文期刊>The European Journal of Neuroscience >Re-examining the ontogeny of substantia nigra dopamine neurons.
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Re-examining the ontogeny of substantia nigra dopamine neurons.

机译:重新检查黑质多巴胺神经元的个体发育。

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Abstract Recently, the need to detail the precise ontogeny of nigrostriatal dopamine neurons has grown significantly. It is now thought that the gestational day on which the majority of these neurons are born is important not only for maximizing the yield of primary cells for transplantation but also for extracting suitable dopamine neural precursors (as stem cells) for expansion in vitro. Historically, peak ontogeny of substantia nigra pars compacta (SNc) dopamine neurons in the rat has been considered to occur around embryonic day (E)14. However, such a concept is at odds with recent studies that reveal not only that substantial numbers of tyrosine hydroxylase-immunopositive cells reside in the ventral mesencephalic region of rats at E14 but that many of these cells have matured extensive axonal projections to the ventral forebrain. Here, then, the ontogeny of SNc neurons in rats commonly used as a source of donor tissue for experimental cell transplantation in animal models of Parkinson's disease has been re-examined. Using a combination of bromodeoxyuridine (BrdU) administration at E11, E12, E13 or E14 with immunocytochemical stainings for both BrdU and tyrosine hydroxylase after 4 weeks of postnatal development, this characterization reveals that the vast majority (perhaps 80%) of SNc dopamine neurons are probably born on E12 in Sprague-Dawley rats. Such findings are important in refining the use of embryonic tissues for primary cell transplantation and may provide more precise timing for identifying the cellular and molecular events that drive neural stem cells toward a dopaminergic phenotype during development.
机译:摘要近来,详细描述黑纹状体多巴胺神经元的精确个体发育的需求已显着增加。现在认为,大多数这些神经元出生的孕期不仅对于最大化用于移植的原代细胞的产量很重要,而且对于提取合适的多巴胺神经前体(作为干细胞)进行体外扩增也很重要。从历史上看,大鼠黑质致密部(SNc)多巴胺神经元的最大个体发育被认为在胚胎发生的第(E)14日左右发生。但是,这种概念与最近的研究相矛盾,后者不仅显示出大量酪氨酸羟化酶免疫阳性细胞存在于E14的大鼠腹侧中脑区域,而且许多这些细胞已经成熟到腹侧前脑的广泛轴突投影。然后,在这里,已经重新检查了通常用作帕金森氏病动物模型中实验细胞移植的供体组织来源的大鼠的SNc神经元的个体发育。在出生后4周后,结合在E11,E12,E13或E14上使用溴脱氧尿苷(BrdU)以及BrdU和酪氨酸羟化酶的免疫细胞化学染色,此特征表明绝大多数(也许80%)SNc多巴胺神经元是可能出生于Sprague-Dawley大鼠的E12。这些发现对于完善胚胎组织在原代细胞移植中的应用很重要,并且可以为鉴定在发育过程中驱动神经干细胞趋向多巴胺能表型的细胞和分子事件提供更精确的时机。

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