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J Cereb Blood Flow Metab. 2012 Apr;32(4):633-42. doi: 10.1038/jcbfm.2011.166. Epub 2011 Nov 30.

Abnormal metabolic brain networks in a nonhuman primate model of parkinsonism.

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  • 1Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA. yma@nshs.edu

Abstract

Parkinson's disease (PD) is associated with a characteristic regional metabolic covariance pattern that is modulated by treatment. To determine whether a homologous metabolic pattern is also present in nonhuman primate models of parkinsonism, 11 adult macaque monkeys with parkinsonism secondary to chronic systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 12 age-matched healthy animals were scanned with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). A subgroup comprising five parkinsonian and six control animals was used to identify a parkinsonism-related pattern (PRP). For validation, analogous topographies were derived from other subsets of parkinsonian and control animals. The PRP topography was characterized by metabolic increases in putamen/pallidum, thalamus, pons, and sensorimotor cortex, as well as reductions in the posterior parietal-occipital region. Pattern expression was significantly elevated in parkinsonian relative to healthy animals (P<0.00001). Parkinsonism-related topographies identified in the other derivation sets were very similar, with significant pairwise correlations of region weights (r>0.88; P<0.0001) and subject scores (r>0.74; P<0.01). Moreover, pattern expression in parkinsonian animals correlated with motor ratings (r>0.71; P<0.05). Thus, homologous parkinsonism-related metabolic networks are demonstrable in PD patients and in monkeys with experimental parkinsonism. Network quantification may provide a useful biomarker for the evaluation of new therapeutic agents in preclinical models of PD.

PMID:
22126913
[PubMed - indexed for MEDLINE]
PMCID:
PMC3318142
Free PMC Article

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