TY - JOUR
T1 - Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease
T2 - An in vivo 11C-raclopride PET study
AU - Politis, Marios
AU - Piccini, Paola
AU - Pavese, Nicola
AU - Koh, Seong Beom
AU - Brooks, David J.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2008/11
Y1 - 2008/11
N2 - A mild to moderate reduction in dopamine, noradrenaline and serotonin levels alongside a progressive loss of hypocretin cells and melanin hormone concentrating cells has been reported in the hypothalamus of PD at postmortem. Hypothalamic uptake of 18F-dopa PET, an in vivo marker of dysfunction of monoaminergic neurons, is also significantly reduced in these patients. These data indicate a general impairment of hypothalamic function in PD. Dopamine receptors play an important role in the regulation of hypothalamic pathways. To date, possible changes in hypothalamic D2 receptor availability have not been investigated in PD. The objective in this study was to assess dopamine D2 receptor availability in hypothalamus of patients with idiopathic Parkinson's disease (PD) using positron emission tomography (PET) with 11C-raclopride (RAC). We evaluated D2 binding in RAC PET images of 14 PD patients using both region of interest (ROI) analysis and a voxel based approach. ROIs for the hypothalamus were traced on the subject's MRI co-registered to the PET image. 11C-raclopride binding potentials (BP) for hypothalamus were obtained by applying ROIs onto parametric images. Findings were compared with those of 9 normal controls. We found a significant reduction in the mean hypothalamic RAC BP of the PD patients compared with the normal controls (0.2714 ± 0.06 vs. 0.3861 ± 0.04; mean ± SD; p = 0.0005). ROI results were confirmed with statistical parametric mapping (SPM). Individual hypothalamic BP values of PD patients did not correlate with age, disease duration, disease severity and levodopa equivalent dose. It remains to be ascertained whether the reductions in hypothalamic D2 receptor availability seen in PD are disease related, the results of chronic exposure to levodopa or both. Our results provide further evidence of dopaminergic dysfunction in the hypothalamus in PD, and this may contribute to the development of sleep, endocrine and autonomic disorders.
AB - A mild to moderate reduction in dopamine, noradrenaline and serotonin levels alongside a progressive loss of hypocretin cells and melanin hormone concentrating cells has been reported in the hypothalamus of PD at postmortem. Hypothalamic uptake of 18F-dopa PET, an in vivo marker of dysfunction of monoaminergic neurons, is also significantly reduced in these patients. These data indicate a general impairment of hypothalamic function in PD. Dopamine receptors play an important role in the regulation of hypothalamic pathways. To date, possible changes in hypothalamic D2 receptor availability have not been investigated in PD. The objective in this study was to assess dopamine D2 receptor availability in hypothalamus of patients with idiopathic Parkinson's disease (PD) using positron emission tomography (PET) with 11C-raclopride (RAC). We evaluated D2 binding in RAC PET images of 14 PD patients using both region of interest (ROI) analysis and a voxel based approach. ROIs for the hypothalamus were traced on the subject's MRI co-registered to the PET image. 11C-raclopride binding potentials (BP) for hypothalamus were obtained by applying ROIs onto parametric images. Findings were compared with those of 9 normal controls. We found a significant reduction in the mean hypothalamic RAC BP of the PD patients compared with the normal controls (0.2714 ± 0.06 vs. 0.3861 ± 0.04; mean ± SD; p = 0.0005). ROI results were confirmed with statistical parametric mapping (SPM). Individual hypothalamic BP values of PD patients did not correlate with age, disease duration, disease severity and levodopa equivalent dose. It remains to be ascertained whether the reductions in hypothalamic D2 receptor availability seen in PD are disease related, the results of chronic exposure to levodopa or both. Our results provide further evidence of dopaminergic dysfunction in the hypothalamus in PD, and this may contribute to the development of sleep, endocrine and autonomic disorders.
KW - 11C-Raclopride
KW - Dopamine D receptors
KW - Dopamine D receptors
KW - Hypothalamus
KW - PD (Parkinson's disease)
KW - PET (positron emission tomography)
KW - Putamen
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U2 - 10.1016/j.expneurol.2008.07.021
DO - 10.1016/j.expneurol.2008.07.021
M3 - Article
C2 - 18723016
AN - SCOPUS:54049120959
SN - 0014-4886
VL - 214
SP - 112
EP - 116
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -