title: Regulation of dopamine D₃ receptor in the striatal regions and substantia nigra in diffuse Lewy body disease.
abstract: The regulation of D₃ receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D₃-preferring radioligand [(3)H]WC-10 and a D₂-preferring radioligand [(3)H]raclopride were used and the absolute densities of the dopamine D₃ and D₂ receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from five cases of DLBD, which included dementia with Lewy bodies (DLB, n=4) and Parkinson disease dementia (PDD, n=1). The densities of the dopamine D₁ receptor, vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. The densities of these dopaminergic markers were also measured in the same brain regions in 10 age-matched control cases. Dopamine D₃ receptor density was significantly increased in the striatal regions including caudate, putamen and nucleus accumbens (NAc). There were no significant changes in the dopamine D₁ and D₂ receptor densities in any brain regions measured. VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however, the significant reduction was found in the putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D₃ receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric states such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations.
authors.affiliation: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Neurosurgery Department, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Neurobiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Occupational Therapy, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Physical Therapy, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Cell Biology & Physiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Mach
authors.affiliation: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA. Electronic address: jinbinxu@wustl.edu.
authors.forename: J
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D010879:Piperazines; D020891:Raclopride; D011877:Radionuclide Imaging; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C543148:WC10 compound; D020891:Raclopride
keywords: Parkinson disease; diffuse Lewy body disease; dopamine receptors; quantitative autoradiography