Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1620, USA.
Eur J Neurol. 2011 May;18(5):703-10. doi: 10.1111/j.1468-1331.2010.03246.x. Epub 2010 Nov 12.
Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the 'catecholaldehyde hypothesis' about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum - especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease - and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease.
Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end-stage Parkinson disease (N=15) and control subjects (N=14) of similar age with similar post-mortem intervals.
Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P=0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients.
Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.
二羟苯乙酮（DOPAL）是多巴胺的细胞毒性代谢产物，是帕金森病发病机制“儿茶酚醛假说”的研究焦点。本研究旨在探讨 DOPAL 是否可在人纹状体中被检测到，尤其是在帕金森病中多巴胺耗竭的主要部位——壳核（Pu），以及它与帕金森病中儿茶酚胺储存和代谢的其他神经化学指标是否相关。
在经病理证实处于疾病终末期的帕金森病患者（n=15）和年龄相近、死后间隔相似的对照组（n=14）的纹状体组织中测量壳核、尾状核（Cd）和额叶皮质（Ctx）儿茶酚的含量。
在所有受试者以及帕金森病组和对照组中，壳核 DOPAL（对照组中多巴胺的 3%）与多巴胺和二羟苯乙酸均呈正相关。帕金森病患者的壳核多巴胺减少了 93%，二羟苯乙酸减少了 95%，而 DOPAL（减少了 83%）和去甲肾上腺素（减少了 73%）在 Pu 中的减少程度较小，多巴胺（减少了 74%）和二羟苯乙酸（减少了 82%）在 Cd 中的减少程度较小。在帕金森病患者中，壳核 DOPAL/二羟苯乙酸的平均值为对照组的 3.4 倍（P=0.03），DOPAL/多巴胺的平均值为对照组的 4.4 倍（P=0.03）。Ctx 中的主要儿茶酚胺是去甲肾上腺素，帕金森病患者的去甲肾上腺素减少了 51%。
帕金森病患者中 DOPAL、多巴胺和二羟苯乙酸的相关性降低反映了 Pu 多巴胺储存的严重丧失，这似乎比 Pu 去甲肾上腺素或 Cd 多巴胺储存的丧失更为广泛。帕金森病患者 Pu 中 DOPAL/二羟苯乙酸比值升高提示醛脱氢酶对 DOPAL 的解毒作用降低。细胞溶质 DOPAL 水平升高可能导致帕金森病中多巴胺能神经元的丧失。
