Inter-hemispheric asymmetry of nigrostriatal dopaminergic lesion: A possible compensatory mechanism in Parkinson's disease
EntityUAM. Departamento de Anatomía, Histología y Neurociencia
10.3389/fnsys.2011.00092Frontiers in Systems Neuroscience 5 (2011): 92
Funded byThis work was supported in part by the Plan Nacional de Investigación (SAF2005-08416; SAF2008-04276), Ministerio de Ciencia e Innovación, and by the UTE-CIMA agreement with the Universidad de Navarra. Carlos Juri was supported by the ALBAN Programme, the European Union Programme of High Level Scholarships for Latin America, scholarship No. E07D403507CL
Subjects18F-DOPA; Compensatory mechanisms; Dopaminergic; MPTP; Parkinson's disease; PET; Medicina
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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 nigros-triatal systems. In preliminary data obtained by our group from asymmetric PD patients, a higherasymmetry index as measured by 6-[ 18F] fluoro-L-dopa ( 18F-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 18F-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
Google Scholar:Blesa, Javier - Juri, Carlos - García-Cabezas, Miguel Ángel - Adánez, Rebeca - Sánchez-González, Miguel Ángel - Cavada, Carmen - Obeso, José Angel
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