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苍白球多巴胺与帕金森病运动亚型:临床与脑生化相关性

Globus pallidus dopamine and Parkinson motor subtypes: clinical and brain biochemical correlation.

作者信息

Rajput A H, Sitte H H, Rajput A, Fenton M E, Pifl C, Hornykiewicz O

机构信息

Division of Neurology, Department of Medicine, University of Saskatchewan/Saskatoon Health Region, Canada.

出版信息

Neurology. 2008 Apr 15;70(16 Pt 2):1403-10. doi: 10.1212/01.wnl.0000285082.18969.3a. Epub 2008 Jan 2.

Abstract

BACKGROUND

Patients with Parkinson disease (PD) may be akinetic/rigid, be tremor dominant, or have comparable severity of these motor symptoms (classic). The pathophysiologic basis of different PD phenotypes is unknown. This study assessed pallidal and striatal dopamine level patterns in different motor subgroups of PD and normal control brains.

METHODS

Globus pallidus and striatum dopamine (DA) levels were measured with high performance liquid chromatography in eight autopsy confirmed PD and five control frozen brains.

RESULTS

DA levels in the external globus pallidus (GPe) of normal brains were nearly six times greater than in the internal pallidum (GPi). In PD, the mean loss of DA was marked (-82%) in GPe and moderate (-51%) in GPi. DA loss of variable degree was seen in different subdivisions of GPe and GPi in PD; however, DA levels were near normal in the ventral (rostral and caudal) GPi of PD cases with prominent tremor. There was marked loss of DA (-89%) in the caudate and severe loss (-98.4%) in the putamen in PD. The pattern of pallidal DA loss did not match the putaminal DA loss.

CONCLUSION

There is sufficient loss of dopamine (DA) in external globus pallidus and the internal globus pallidum (GPi) as may contribute to the motor manifestations of Parkinson disease (PD). The possible functional disequilibrium between GABAergic and DAergic influences in favor of DA in the caudoventral parts of the GPi may contribute to resting tremor in tremor dominant and classic PD cases.

摘要

背景

帕金森病(PD)患者可能表现为运动不能/强直型、震颤为主型,或这些运动症状的严重程度相当(典型型)。不同PD表型的病理生理基础尚不清楚。本研究评估了PD不同运动亚组及正常对照大脑中苍白球和纹状体的多巴胺水平模式。

方法

采用高效液相色谱法测量8例尸检确诊的PD患者和5例对照者冷冻大脑中的苍白球和纹状体多巴胺(DA)水平。

结果

正常大脑外侧苍白球(GPe)中的DA水平几乎是内侧苍白球(GPi)的6倍。在PD患者中,GPe中DA的平均损失显著(-82%),而GPi中的损失为中度(-51%)。在PD患者的GPe和GPi不同亚区可见不同程度的DA损失;然而,在震颤明显的PD患者的腹侧(喙侧和尾侧)GPi中,DA水平接近正常。PD患者尾状核中的DA损失显著(-89%),壳核中的损失严重(-98.4%)。苍白球DA损失模式与壳核DA损失不匹配。

结论

外侧苍白球和内侧苍白球(GPi)中多巴胺(DA)的充分损失可能导致帕金森病(PD)的运动表现。在GPi尾腹侧部分,GABA能和DA能影响之间可能存在有利于DA的功能失衡,这可能导致震颤为主型和典型PD患者的静止性震颤。

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