title: Abnormal metabolic brain networks in a nonhuman primate model of parkinsonism.
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.
authors: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA. yma@nshs.edu
authors: Yilong
authors: Y
authors: Ma
authors: Shichun
authors: S
authors: Peng
authors: Phoebe G
authors: PG
authors: Spetsieris
authors: Vesna
authors: V
authors: Sossi
authors: David
authors: D
authors: Eidelberg
authors: Doris J
authors: DJ
authors: Doudet
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D008251:Macaca; D008297:Male; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011699:Putamen / Q000378:metabolism* / Q000473:pathology; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology
chemical_list: D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine