Inter-hemispheric asymmetry of nigrostriatal dopaminergic lesion: a possible compensatory mechanism in Parkinson's disease
Inter-hemispheric asymmetry of nigrostriatal dopaminergic lesion: a possible compensatory mechanism in Parkinson's disease
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DOI：
10.3389/fnsys.2011.00092
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发表时间：
2011-01-01
影响因子：
3
通讯作者：
Obeso, Jose A.
中科院分区：
文献类型：
--
作者：
Blesa, Javier;Juri, Carlos;Obeso, Jose A.
帕金森病（PD）的发病特点是在一个身体部位的局灶性运动功能，这通常与对侧后壳核的多巴胺能消耗更大。然而，多巴胺（DA）半球差异在PD运动症状的发作和进展中的作用仍不明确。以往的研究表明，单方面操纵一个黑质纹状体系统影响对侧DA营业额，表明功能和补偿性的相互依赖的两个黑质纹状体系统。在我们小组从不对称PD患者获得的初步数据中，通过6-[F-18]氟-L-多巴（F-18-DOPA）正电子发射断层扫描（PET）测量的较高不对称指数与较高阈值（即，更大的多巴胺能损失）的发病运动症状在较少受影响的一面。为了进一步阐明这一点的基础，我们进行了一项补充研究，在猴子使用PET评估和相关的多巴胺能纹状体耗竭的程度与运动活动。对照组和1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）中毒的猴子与对称的病变进行了表征行为和F-18-DOPA PET。同时，在一只猴的黑质纹状体投射单侧造成急性病变，在同侧纹状体产生30%的多巴胺能耗竭，这与任何明显的帕金森病特征或缺陷无关。这只猴子几个月来一直没有症状。随后，该猴接受全身MPTP，随后在帕金森病体征进展期间重复评价运动行为和PET。使用免疫组织化学方法处理所有猴子的大脑。我们的研究结果表明，运动体征的发生与受影响较小的对侧纹状体的多巴胺能状态有关并受其影响。虽然这项工作仍是初步的，但该研究同意我们的一般假设，即在PD纹状体DA缺陷的补偿中，半球相互依赖
The onset of Parkinson's disease (PD) is characterized by focal motor features in one body part, which are usually correlated with greater dopaminergic depletion in the contralateral posterior putamen. The role of dopamine (DA) hemispheric differences in the onset and progression of motor symptoms of PD, however, remains undefined. Previous studies have demonstrated that unilateral manipulations of one nigrostriatal system affect contralateral DA turnover, indicating a functional and compensatory inter-dependence of the two nigrostriatal systems. In preliminary data obtained by our group from asymmetric PD patients, a higher asymmetry index as measured by 6-[F-18]fluoro-L-dopa (F-18-DOPA) positron emission tomography (PET) was associated with a higher threshold (i.e., greater dopaminergic loss) for the onset of motor symptoms in the less-affected side. To further elucidate the underlying basis for this, we carried out a complementary study in monkeys using PET to assess and correlate the degree of dopaminergic striatal depletion with motor activity. Control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated monkeys with symmetrical lesions were characterized behaviorally and with F-18-DOPA PET. In parallel, an acute lesion was inflicted in the nigrostriatal projection unilaterally in one monkey, generating a 30% dopaminergic depletion in the ipsilateral striatum, which was not associated with any noticeable parkinsonian feature or deficit. The monkey remained asymptomatic for several months. Subsequently, this monkey received systemic MPTP, following which motor behavior and PET were repeatedly evaluated during progression of parkinsonian signs. The brains of all monkeys were processed using immunohistochemical methods. Our results suggest that the onset of motor signs is related to and influenced by the dopaminergic status of the less-affected, contralateral striatum. Although this work is still preliminary, the study agrees with our general hypothesis of hemispheric inter-dependence in the compensation of striatal DA deficit in PD