期刊
NEUROIMAGE-CLINICAL
卷 18, 期 -, 页码 433-442出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2018.02.010
关键词
Parkinson's disease; Dopamine; Positron emission tomography (PET); Neurodegeneration; Fallypride
类别
资金
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01NS097783, K23NS080988]
- National Institute of Aging [R01AG044838]
- CTSA award from the National Center for Advancing Translational Sciences [UL1TR000445]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD083211] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS097783] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [F32DA041157] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD019963] Funding Source: NIH RePORTER
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D-2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D-2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D-2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age-and sex-matched healthy controls (HCs) using PET imaging with [F-18] fallypride, a high affinity D-2/3 receptor ligand, to measure striatal and extrastriatal D-2/3 nondisplaceable binding potential (BPND). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BPND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D-2/3 receptors, where reduced BPND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D-2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D-2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.
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