TY - JOUR
T1 - Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease
AU - Sun, J.
AU - Cairns, N. J.
AU - Perlmutter, J. S.
AU - Mach, R. H.
AU - Xu, J.
N1 - Funding Information:
This study was supported by NIH Grants MH081281, DA29840, NS075321 and P50 AG05681, the American Parkinson Disease Association (APDA), the Greater St. Louis Chapter of the APDA, the Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund) and the Charles and Joanne Knight Alzheimer’s Research Initiative of the Washington University Alzheimer’s Disease Research Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no competing financial interests.
PY - 2013/9/17
Y1 - 2013/9/17
N2 - The regulation of D3 receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D3-preferring radioligand [3H]WC-10 and a D2-preferring radioligand [3H]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 [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]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.
AB - The regulation of D3 receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D3-preferring radioligand [3H]WC-10 and a D2-preferring radioligand [3H]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 [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]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.
KW - Diffuse Lewy body disease
KW - Dopamine receptors
KW - Parkinson disease
KW - Quantitative autoradiography
UR - http://www.scopus.com/inward/record.url?scp=84880164665&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2013.05.048
DO - 10.1016/j.neuroscience.2013.05.048
M3 - Article
C2 - 23732230
AN - SCOPUS:84880164665
SN - 0306-4522
VL - 248
SP - 112
EP - 126
JO - Neuroscience
JF - Neuroscience
ER -