Goldstein David S, Sullivan Patti, Holmes Courtney, Mash Deborah C, Kopin Irwin J, Sharabi Yehonatan
Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, Bethesda, MD 20892-1620, USA.
Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, Bethesda, MD 20892-1620, USA.
Parkinsonism Relat Disord. 2017 Feb;35:88-91. doi: 10.1016/j.parkreldis.2016.12.011. Epub 2016 Dec 15.
Severe putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA.
Post-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA).
The PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p < 0.0001). An index of innervation (the sum of DOPA + Cys-DOPA) averaged 63% of control (p = 0.01).
Based on patterns of parent and cysteinyl catechols in putamen, PD and MSA involve decreased vesicular uptake and decreased LAAAD activity in the residual dopaminergic terminals. The combination seems to contribute importantly to dopamine depletion in these diseases.
严重的壳核多巴胺耗竭是帕金森病（PD）和多系统萎缩（MSA）的特征。这种耗竭的程度大于仅由黑质纹状体多巴胺能终末丧失所能解释的程度。我们利用壳核组织中儿茶酚及其半胱氨酸衍生物的水平和比例，来探究PD和MSA中多巴胺合成及代谢可能存在的与去神经无关的异常情况。5-S-半胱氨酰多巴（Cys-DOPA）由多巴的自发氧化产生，5-S-半胱氨酰多巴胺（Cys-DA）由多巴胺的自发氧化产生。
对17例PD患者、25例MSA患者及30例对照的尸检壳核组织样本进行检测，分析其中的内源性儿茶酚，包括多巴胺（DA）、其胞质代谢产物（Cys-DA、3,4-二羟基苯乙酸、3,4-二羟基苯乙醇及3,4-二羟基苯乙醛），以及DA上游的酪氨酸羟化产物（多巴和Cys-DOPA）。
PD组和MSA组中儿茶酚及其半胱氨酸衍生物的平均值无差异，两组数据合并分析。患者中DA的囊泡储存指标（DA与其胞质代谢产物总和的比值）平均为对照组的54%（p = 0.001），L-芳香族氨基酸脱羧酶（LAAAD）活性指标（DA及其胞质代谢产物总和与多巴 + Cys-DOPA总和的比值）平均为对照组的21%（p < 0.0001）。神经支配指标（多巴 + Cys-DOPA总和）平均为对照组的63%（p = 0.01）。
基于壳核中儿茶酚及其半胱氨酸衍生物的模式，PD和MSA涉及残余多巴胺能终末的囊泡摄取减少和LAAAD活性降低。这种组合似乎在这些疾病的多巴胺耗竭中起重要作用。
