Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease

被引:52
作者
Piggott, MA
Owens, J
O'Brien, J
Colloby, S
Fenwick, J
Wyper, D
Jaros, E
Johnson, M
Perry, RH
Perry, EK
机构
[1] Univ Newcastle, MRC, Ctr Clin Brain Ageing, Newcastle Gen Hosp, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England
[2] N Glasgow Univ Hosp NHS Trust, Western Infirm, W Scotland Radionuclide Dispensary, Glasgow G11 6NT, Lanark, Scotland
[3] Newcastle Gen Hosp, Wolfson Res Ctr, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England
[4] So Gen Hosp, S Glasgow Univ Hosp NHS Trust, Dept Clin Phys, Glasgow G51 4TF, Lanark, Scotland
关键词
SPET imaging; 3-quinuclidinyl-4-iodobenzilate; autoradiography; pirenzepine; AF-DX; 384; cholinergic therapy;
D O I
10.1016/S0891-0618(03)00002-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Derivatives of the muscarinic antagonist 3-quinuclidinyl-4-iodobenzilate (QNB), particularly [I-123]-(R,R)-I-QNB, are currently being assessed as in vivo ligands to monitor muscarinic receptors in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), relating changes to disease symptoms and to treatment response with cholinergic medication. To assist in the evaluation of in vivo binding. muscarinic receptor density in post-mortem human brain was measured by autoradiography with [I-125]-(R,R)-I-QNB and [I-125]-(R,S)-I-QNB and compared to M1 ([H-3]pirenzepine) and M2 and M4 ([H-3]AF-DX 384) receptor binding. Binding was calculated in tissue containing striatum, globus pallidus (GPe), claustrum, and cingulate and insula cortex, in cases of AD, DLB, Parkinson's disease (PD) and normal elderly controls. Pirenzepine, AF-DX 384 and (R,S)-I-QNB binding in the striatum correlated positively with increased Alzheimer-type pathology, and AF-DX 384 and (R,R)-I-QNB cortical binding correlated positively with increased Lewy body (LB) pathology, however, striatal pirenzepine binding correlated negatively with cortical LB pathology. M I receptors were significantly reduced in striatum in DLB compared to AD, PD, and controls and there was a significant correlation between M1 and dopamine D2 receptor densities. [H-3]AF-DX 384 binding was higher in the striatum and GPe in AD. Binding of [I-125]-( R,R)-I-QNB, which may reflect increased muscarinic M4 receptors, was higher in cortex and claustrum in DLB and AD. [I-125]-(R,S)-I-QNB binding was higher in the GPe in AD. Low M1 and D2 receptors in DLB imply altered regulation of the striatal projection neurons which express these receptors. Low density of striatal M1 receptors may relate to the extent of movement disorder in DLB, and to a reduced risk of parkinsonism with acetylcholinesterase inhibition. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:161 / 173
页数:13
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