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Age differences in muscarinic cholinergic receptors assayed with (+) N ‐[ 11 C]methyl‐3‐piperidyl benzilate in the brains of conscious monkeys
Author(s) -
Tsukada Hideo,
Kakiuchi Takeharu,
Nishiyama Shingo,
Ohba Hiroyuki,
Sato Kengo,
Harada Norihiro,
Takahashi Kazuhiro
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1082
Subject(s) - in vivo , muscarinic acetylcholine receptor , cholinergic , chemistry , endocrinology , medicine , receptor , metabolite , striatum , biology , biochemistry , dopamine , microbiology and biotechnology
Age‐related changes in muscarinic cholinergic receptors were evaluated with the novel ligand (+) N ‐[ 11 C]methyl‐3‐piperidyl benzilate ((+)3‐MPB) in the living brains of young (5.9 ± 1.8 years old) and aged (19.0 ± 3.3 years old) monkeys ( Macaca mulatta ) in the conscious state using high‐resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo, metabolite‐corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and kinetic analyses using the three‐compartment model and graphical Logan plot analysis were applied. Kinetic analyses of [ 11 C](+)3‐MPB indicated a regionally specific decrease in the receptor binding in vivo determined as binding potential (BP) = k 3 /k 4 in aged animals compared with young animals. Thus, the frontal and temporal cortices as well as the striatum showed age‐related reduction of muscarinic cholinergic receptors in vivo, reflecting the reduced receptor density (B max ) determined by Scatchard plot analysis in vivo. In the hippocampus, although BP of [ 11 C](+)3‐MPB indicated no significant age‐related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the graphical Logan plot analysis was applied, all regions assayed showed significant age‐related decrease of [ 11 C](+)3‐MPB binding. These results demonstrate the usefulness of kinetic three‐compartment model analysis of [ 11 C](+)3‐MPB with metabolite‐corrected arterial plasma input as an indicator for the aging process of the cortical muscarinic cholinergic receptors in vivo as measured by PET. Synapse 41:248–257, 2001. © 2001 Wiley‐Liss, Inc.