Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid.
Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid.
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纹状体和脑脊液中多巴胺耗竭和代偿反应的标志物。
DOI：
10.1007/bf02252962
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Matson,WR
中科院分区：
文献类型：
--
作者：
Loeffler,DA;LeWitt,PA;DeMaggio,AJ;Juneau,PL;Milbury,PE;Matson,WR
虽然CSF高香草酸（HVA）浓度的耗竭通常被认为是帕金森病（PD）多巴胺（DA）缺乏的直接指标，但CSF HVA在轻度受累患者中是正常的。为了探索原因，我们测量了DA及其代谢产物在纹状体和CSF中的兔子接受利血平5天。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周转的代偿性增加。在纹状体DA的96%耗竭，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）下降64%和92%，在纹状体，虽然最终产品，HVA，是不变的。相反，CSF中HVA和DOPAC的浓度显著增加，但3-MT和左旋多巴（LD）没有改变。利血平诱导DA耗竭后纹状体LD浓度升高5倍，为DA合成增强提供了证据。在PD中，利血平给药后DA合成的代偿性增加混淆了CSF HVA反映DA耗竭的能力。
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.