Age-dependent decline of steady state dopamine storage capacity of human brain: An FDOPA PET study
Age-dependent decline of steady state dopamine storage capacity of human brain: An FDOPA PET study
复制标题
DOI：
10.1016/j.neurobiolaging.2008.05.005
复制
发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Cumming, Paul
中科院分区：
文献类型：
--
作者：
Kumakura, Yoshitaka;Vernaleken, Ingo;Cumming, Paul
活体人脑中多巴胺利用的常规指标并没有一致地显示多巴胺功能随着正常衰老而显著下降。然而，大多数动力学分析方法都假设脱羧FDOPA代谢物在大脑中不可逆捕获，即使在短时间的PET记录中也违反了这一假设。因此，我们开发了计算FDOPA及其脱羧代谢物（V-d, ml g(-1)）稳态储存的方法，基于改进的120分钟排放记录的动力学分析。在一组28名年龄从23岁到73岁的正常男性受试者中，纹状体和纹状体外区的V-d幅度每十年下降约10%。FDOPA的利用率也通过几种假设不可逆捕获的传统方法计算，即净血脑清除率(k -in(app), ml g(-1) min(-1))，相对于参考组织输入的DOPA脱羧酶活性(k(3)(S), min(-1))，以及相对于动脉输入的DOPA脱羧酶活性(k（3), min(-1)）。这些方法都没有发现扩展纹状体中FDOPA利用的年龄相关下降，尽管大脑皮层中K-in（app）的水平确实下降了。因此，在老年受试者的纹状体中，合成[F-18]氟多巴胺的能力基本保持不变，但冲洗率（k(loss)）大幅增加，这在所有被检查的大脑区域都很明显。因此，V-d的大小随着健康年龄的增长而下降，可能反映了囊泡储存能力受损，导致胞质[F-18]氟多巴胺对单胺氧化酶的暴露增加。(C) 2008爱思唯尔公司版权所有。
Conventional indices of the utilization of FDOPA in living human brain have not consistently revealed important declines in dopamine function with normal aging. However, most methods of kinetic analysis have assumed irreversible trapping of decarboxylated FDOPA metabolites in brain, an assumption that is violated even in PET recordings of short duration. Therefore, we have developed methods for the calculation of steady-state storage of FDOPA together with its decarboxylated metabolites (V-d, ml g(-1)), based upon improved kinetic analysis of 120-min emission recordings. In a group of 28 normal male subjects, of age ranging from 23 to 73 years, the magnitude of V-d in the striatum and in extrastriatal regions declined by approximately 10% with each decade. The utilization of FDOPA was also calculated by several conventional methods assuming irreversible trapping, i.e. the net blood brain clearance (K-in(app), ml g(-1) min(-1)), the DOPA decarboxylase activity relative to a reference tissue input (k(3)(S), min(-1)), and relative to the arterial input (k(3)(D), min(-1)). None of these methods revealed an age-related decline in FDOPA utilization in the extended striatum, although the magnitude of K-in(app) did decline in cerebral cortex. Thus, the capacity to synthesize [F-18]fluorodopamine remained largely intact in striatum of the elderly subjects, but in the presence of a substantially increased rate of washout (k(loss)), which was evident in all brain regions examined. Consequently, the magnitude of V-d declined with healthy aging, possibly reflecting impaired vesicular storage capacity, resulting in enhanced exposure of cytosolic [F-18]fluorodopamine to monoamine oxidase. (C) 2008 Elsevier Inc. All rights reserved.