Age-related changes in binding of the D2/3 receptor radioligand [11C](+) PHNO in healthy volunteers
Age-related changes in binding of the D2/3 receptor radioligand [11C](+) PHNO in healthy volunteers
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DOI：
10.1016/j.neuroimage.2016.02.002
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发表时间：
2016-04-15
期刊：
影响因子：
5.7
通讯作者：
Carson, Richard E.
中科院分区：
文献类型：
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作者：
Matuskey, David;Worhunksy, Patrick;Carson, Richard E.
目的：之前的正电子发射断层扫描（PET）成像研究已经可靠地证明了多巴胺系统与年龄相关的下降。这些研究中的大多数都集中在纹状体中多巴胺受体亚型D2/3R（D2 R家族）的密度上，使用对D（2）Rvs基本上无选择性的拮抗剂放射性示踪剂。D3 R亚型。因此，对富含D-3的纹状体外区（如黑质/腹侧被盖区（SN/VTA）和下丘脑）的任何可能的年龄效应知之甚少。本研究试图调查是否与[C-11]（+）PHNO，D3 R-偏好激动剂放射性示踪剂，测量受体的可用性，也随着age.Methods下降：42名健康对照受试者（9名女性，33名男性;年龄范围19-55岁）进行扫描与[C-11]（+）PHNO使用高分辨率研究断层扫描仪（HRRT）。使用简化参考组织模型（SRTM 2）以小脑为参考区域计算参数图像。计算杏仁核、尾状核、下丘脑、苍白球、壳核、SN/VTA、丘脑和腹侧纹状体的结合电位（BPND），然后在体素水平上用全脑参数图像进行确认。区域性[C-11]（+）PHNO BPND显示尾状核受体可用性与年龄呈负相关健康受试者的壳核（r=-0.56，校正p=0.0008）和壳核（r=-0.45，校正p= 0.02）（每十年分别降低8%和5%）。年龄与其他脑区（包括下丘脑和SN/VTA）之间无显著相关性。二次全脑体素明智的分析证实了这些投资回报率的负相关性，并进一步确定了中脑（SN/VTA）regions.Conclusion的正相关性：按照以前的研究，纹状体（一个地区丰富的D2 R）与年龄相关的多巴胺系统下降。我们最初没有发现SN/VTA和下丘脑随年龄变化的证据，这些区域先前发现具有主要的D3 R信号，用[C-11]（+）PHNO测量。二次分析确实发现了中脑（SN/VTA）区域的显著正相关性，表明衰老可能存在差异效应，即D2 R受体可用性随年龄而降低，而D3 R可用性保持不变或增加。(C)2016 Elsevier Inc. All rights reserved.
Objective: Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D2/3R (D2R family) in the striatum using antagonist radiotracers that are largely nonselective for D(2)Rvs. D3R subtypes. Therefore, less is known about any possible age effects in D-3-rich extrastriatal areas such as the substantia nigra/ventral tegmental area (SN/VTA) and hypothalamus. This study sought to investigate whether the receptor availability measured with [C-11](+) PHNO, a D3R-preferring agonist radiotracer, also declines with age.Methods: Forty-two healthy control subjects (9 females, 33 males; age range 19-55 years) were scanned with [C-11](+) PHNO using a High Resolution Research Tomograph (HRRT). Parametric images were computed using the simplified reference tissue model (SRTM2) with cerebellum as the reference region. Binding potentials (BPND) were calculated for the amygdala, caudate, hypothalamus, pallidum, putamen, SN/VTA, thalamus, and ventral striatum and then confirmed at the voxel level with whole-brain parametric images.Results: Regional [C-11](+) PHNO BPND displayed a negative correlation between receptor availability and age in the caudate (r=-0.56, corrected p=0.0008) and putamen (r=-0.45, corrected p= 0.02) in healthy subjects (respectively 8% and 5% lower per decade). No significant correlations with age were found between age and other regions (including the hypothalamus and SN/VTA). Secondary whole-brain voxel-wise analysis confirmed these ROI findings of negative associations and further identified a positive correlation in midbrain (SN/VTA) regions.Conclusion: In accordance with previous studies, the striatum (an area rich in D2R) is associated with age-related declines of the dopamine system. We did not initially find evidence of changes with age in the SN/VTA and hypothalamus, areas previously found to have a predominantly D3R signal as measured with [C-11](+) PHNO. A secondary analysis did find a significant positive correlation in midbrain (SN/VTA) regions, indicating that there may be differential effects of aging, whereby D2R receptor availability decreases with age while D3R availability stays unchanged or is increased. (C) 2016 Elsevier Inc. All rights reserved.