Browsing by Author "Collantes, Maria"

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    Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism
    (2022) Molinet-Dronda, Francisco; Blesa, Javier; Lopez-Gonzalez del Rey, Natalia; Juri, Carlos; Collantes, Maria; Pineda-Pardo, Jose A.; Trigo-Damas, Ines; Iglesias, Elena; Hernandez, Ledia F.; Rodriguez-Rojas, Rafael; Gago, Belen; Ecay, Margarita; Prieto, Elena; Garcia-Cabezas, Miguel A.; Cavada, Carmen; Rodriguez-Oroz, Maria C.; Penuelas, Ivan; Obeso, Jose A.
    Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([C-11]-dihydrotetrabenazine; C-11-DTBZ) and metabolic (2-[F-18]-fluoro-2-deoxy-D-glucose; F-18-FDG) radiotracers. C-11-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. F-18-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
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    Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An F-18-DOPA and C-11-DTBZ PET study
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2010) Blesa, Javier; Juri, Carlos; Collantes, Maria; Penuelas, Ivan; Prieto, Elena; Iglesias, Elena; Marti Climent, Josep; Arbizu, Javier; Zubieta, Jose L.; Cruz Rodriguez Oroz, Mari; Garcia Garcia, David; Richter, Jose A.; Cavada, Carmen; Obeso, Jose A.
    Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic depletion in PD, "in vivo" data concerning the stages of this process are still scarce. We evaluated 6-[18F]-fluoro-L-DOPA (F-18-DOPA) and 11C-(+)-alpha-dihydrotetrabenazine (C-11-DTBZ) using PET in a model of chronically MFTP-induced parkinsonism in non-human primates. Methods: Sixty-seven cynomolgus monkeys (Macaca fascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. Results: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with C-11-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. Conclusions: Serial assessment with F-18-DOPA and C-11-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments. (C) 2010 Elsevier Inc. All rights reserved.
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    Statistical parametric maps of 18F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study
    (2011) Prieto, Elena; Collantes, Maria; Delgado, Mercedes; Juri, Carlos; Garcia-Garcia, Luis; Molinet, Francisco; Fernandez-Valle, Maria E.; Pozo, Miguel A.; Gago, Belen; Marti-Climent, Josep M.; Obeso, Jose A.; Penuelas, Ivan
    Purpose Although specific positron emission tomography (PET) scanners have been developed for small animals, spatial resolution remains one of the most critical technical limitations, particularly in the evaluation of the rodent brain. The purpose of the present study was to examine the reliability of voxel-based statistical analysis (Statistical Parametric Mapping, SPM) applied to F-18-fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal PET not specifically designed for rodents. The gold standard for the validation of the PET results was the autoradiography of the same animals acquired under the same physiological conditions, reconstructed as a 3-D volume and analysed using SPM.