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Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study.
Exp Neurol. 2008 Nov; 214(1):112-6.EN

Abstract

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.

Authors+Show Affiliations

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.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18723016

Citation

Politis, Marios, et al. "Evidence of Dopamine Dysfunction in the Hypothalamus of Patients With Parkinson's Disease: an in Vivo 11C-raclopride PET Study." Experimental Neurology, vol. 214, no. 1, 2008, pp. 112-6.
Politis M, Piccini P, Pavese N, et al. Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study. Exp Neurol. 2008;214(1):112-6.
Politis, M., Piccini, P., Pavese, N., Koh, S. B., & Brooks, D. J. (2008). Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study. Experimental Neurology, 214(1), 112-6. https://doi.org/10.1016/j.expneurol.2008.07.021
Politis M, et al. Evidence of Dopamine Dysfunction in the Hypothalamus of Patients With Parkinson's Disease: an in Vivo 11C-raclopride PET Study. Exp Neurol. 2008;214(1):112-6. PubMed PMID: 18723016.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson's disease: an in vivo 11C-raclopride PET study. AU - Politis,Marios, AU - Piccini,Paola, AU - Pavese,Nicola, AU - Koh,Seong-Beom, AU - Brooks,David J, Y1 - 2008/08/06/ PY - 2008/04/12/received PY - 2008/06/28/revised PY - 2008/07/22/accepted PY - 2008/8/30/pubmed PY - 2010/7/22/medline PY - 2008/8/30/entrez SP - 112 EP - 6 JF - Experimental neurology JO - Exp Neurol VL - 214 IS - 1 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 (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. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/18723016/Evidence_of_dopamine_dysfunction_in_the_hypothalamus_of_patients_with_Parkinson's_disease:_an_in_vivo_11C_raclopride_PET_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(08)00300-2 DB - PRIME DP - Unbound Medicine ER -