Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study.
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 (18)F-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 D(2) receptor availability have not been investigated in PD. The objective in this study was to assess dopamine D(2) receptor availability in hypothalamus of patients with idiopathic Parkinson's disease (PD) using positron emission tomography (PET) with (11)C-raclopride (RAC). We evaluated D(2) 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. (11)C-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 D(2) 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.
Politis
Marios
M
Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Cyclotron Building, Hammersmith Hospital, Imperial College London, DuCane Road W12 0NN, London, UK. marios.politis@imperial.ac.uk
Piccini
Paola
P
Pavese
Nicola
N
Koh
Seong-Beom
SB
Brooks
David J
DJ
D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine