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The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson’s disease

机译:帕金森氏病大鼠模型中腹中脑移植物中的A9多巴胺神经元成分是恢复运动功能的重要决定因素

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摘要

Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson’s disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson’s disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson’s disease. Analysis at the histological level indicates that this is likely to be due to the unique ability of A9 neurons to innervate and functionally activate their target structure, the dorsolateral region of the host striatum. The findings highlight dopamine neuronal subtype composition as a potentially important parameter to monitor in order to understand the variable nature of functional outcome better in transplantation studies. Furthermore, the results have interesting implications for current efforts in this field to generate well-characterized and standardized preparations of transplantable dopamine neuronal progenitors from stem cells.
机译:已知用于帕金森氏病细胞替代疗法的胎儿腹侧中脑移植物中含有多巴胺神经元亚型的混合物,包括黑质的A9神经元和腹侧被盖区的A10神经元。但是,这些亚型对于帕金森氏病影响的大脑功能修复的相对重要性尚未得到充分研究。在这里,我们报告了一系列移植实验的结果,其中比较了选择性缺乏A9神经元或具有典型A9 / A10组成的移植物的解剖学和功能特性。结果表明,在帕金森氏病的啮齿动物模型中,纹状体移植物中的A9成分对于运动能力测试中的恢复至关重要。组织学分析表明,这很可能是由于A9神经元神经支配并功能激活其靶结构(宿主纹状体背外侧区域)的独特能力。这些发现突出了多巴胺神经元亚型组成作为监测潜在的重要参数,以便更好地了解移植研究中功能结果的可变性。此外,该结果对于该领域当前的努力产生了有趣的启示,以从干细胞中产生可移植的多巴胺神经元祖细胞的特征明确和标准化的制剂。

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