Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT
Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT
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DOI：
10.1016/j.neurobiolaging.2007.12.008
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
van Dyck, Christopher H.
中科院分区：
文献类型：
--
作者：
Mitsis, Effie A.;Cosgrove, Kelly P.;van Dyck, Christopher H.
人类尸检研究报告称，大脑中高亲和力尼古丁结合随着年龄的增长而减少。我们使用配体 [I-123]5-IA-85380 ([I-123]5-IA) 和单光子发射计算机断层扫描 (SPECT) 研究了年龄对活体人类受试者八个大脑区域中含 β(2) 烟碱乙酰胆碱受体 (β(2)-nAChR) 可用性的影响。年龄从 18 岁到 85 岁的健康非吸烟者 (N=47) 使用推注加恒定输注模式给予 [I-123]5-IA-，并在平衡条件下 6-8 小时后进行成像。使用线性回归和 Pearson 相关性 (r) 分析年龄对区域 β(2)-nAChR 可用性的影响（V-T，区域脑活动/游离血浆母体，与结合电位成比例的测量）。在所分析的 8 个大脑区域中，有 7 个区域的年龄和区域 β(2)-nAChR 可用性呈负相关，在成人寿命期间下降幅度从 32%（丘脑）到 18%（枕叶皮层）不等，或每十年最多下降 5%。这些在活人受试者中的结果证实了死后报告，即高亲和力尼古丁结合随着年龄的增长而下降，并可能有助于阐明 β(2)-nAChR 在认知衰老中的作用。 (C) 2007 Elsevier Inc. 保留所有权利。
Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on beta(2)-containing nicotinic acetylcholine receptor (beta(2)-nAChR) availability in eight brain regions of living human subjects using the ligand [I-123]5-IA-85380 ([I-123]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N=47) ranging in age from 18 to 85 were administered [I-123]5-IA- using a bolus plus constant infusion paradigm and imaged 6-8 h later under equilibrium conditions. The effect of age on regional beta(2)-nAChR availability (V-T, regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson's correlation (r). Age and regional beta(2)-nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of beta(2)-nAChRs in cognitive aging. (C) 2007 Elsevier Inc. All rights reserved.