Principal, ExVivos, LLC, Hastings-on-Hudson, NY, USA.
J Parkinsons Dis. 2021;11(3):1011-1018. doi: 10.3233/JPD-212715.
The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported.
Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson's disease.
A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels.
Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson's to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p = 0.51 and p = 0.12, respectively) and in the putamen from 0.75 to 4.61 (p = 0.40 and 0.001, respectively).
Free, intracellular dopamine levels are not reduced in Parkinson's disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.
帕金森病的标志是基底神经节中多巴胺的耗竭。帕金森病的模型包括多巴胺作为疾病进展的一个促成因素。然而,尚未报道神经元内的多巴胺水平。
利用荟萃分析方法确定帕金森病中的细胞内多巴胺水平。
对文献进行系统回顾和频率主义荟萃分析。对细胞和轴突数量以及 VMAT2 蛋白水平进行了多巴胺水平的标化。
证实了组织多巴胺、多巴胺能细胞体和 VMAT2 蛋白减少。帕金森氏症与正常大脑细胞内多巴胺的比值,无论是根据细胞数量还是轴突数量进行标化,同时考虑尾状核中的 VMAT2 水平,范围从 1.49 到 1.87(p=0.51 和 p=0.12,分别)和壳核中从 0.75 到 4.61(p=0.40 和 0.001,分别)。
与正常人相比,帕金森病患者细胞内游离多巴胺水平并未以与总组织浓度相似的程度降低,这支持了调节 VMAT2、神经黑色素和/或多巴胺合成作为合理神经保护策略的相关性。