Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid.

D A Loeffler, P A LeWitt, A J DeMaggio, P L Juneau, P E Milbury, W R Matson
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引用次数: 18

Abstract

Though depletion of CSF homovanillic acid (HVA) concentration has often been regarded as a direct indicator of dopamine (DA) deficiency in Parkinson's Disease (PD), CSF HVA is normal in mildly affected patients. To explore why, we measured DA and its metabolites in striatum and CSF in rabbits receiving reserpine for 5 days. Reserpine, which depletes striatal DA by disrupting vesicular storage of the neurotransmitter, results in a compensatory increase of DA turnover. In response to a 96% depletion of striatal DA, its catabolic intermediates 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) decreased 64% and 92% in striatum, although the endproduct, HVA, was unchanged. In contrast, CSF concentrations of HVA and DOPAC increased significantly, though 3-MT and levodopa (LD) were unaltered. A 5-fold rise in striatal LD concentration after reserpine-induced DA depletion provided evidence for enhanced DA synthesis. As in PD, the compensatory increase of DA synthesis after reserpine administration confounds the ability of CSF HVA to reflect DA depletion.

纹状体和脑脊液中多巴胺耗竭和代偿反应的标志物。
虽然脑脊液同型香草酸(HVA)浓度的减少通常被认为是帕金森病(PD)患者多巴胺(DA)缺乏的直接指标,但脑脊液HVA在轻度发病患者中是正常的。为了探究其中的原因,我们测量了接受利血平治疗5天的家兔纹状体和脑脊液中的DA及其代谢物。利血平通过破坏神经递质的囊泡储存来消耗纹状体DA,导致DA周转量代偿性增加。纹状体DA消耗96%后,其分解代谢中间体3,4-二羟基苯乙酸(DOPAC)和3-甲氧基酪胺(3- mt)在纹状体中分别减少64%和92%,但终产物HVA不变。相比之下,脑脊液HVA和DOPAC浓度显著升高,但3-MT和左旋多巴(LD)不变。利血平诱导的DA耗竭后纹状体LD浓度上升5倍,为DA合成增强提供了证据。与帕金森病一样,给予利血平后DA合成代偿性增加混淆了脑脊液HVA反映DA消耗的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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