Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies

Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies
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DOI:
10.1038/jcbfm.2013.19
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发表时间:
2013-06-01
影响因子:
6.3
通讯作者:
Kish, Stephen J.
Kish, Stephen J.
中科院分区:
医学1区
文献类型:
--
作者:
Tong, Junchao;Meyer, Jeffrey H.;Kish, Stephen J.

文献摘要

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考虑到单胺氧化酶在人类神经精神疾病中的临床重要性,单胺氧化酶(MAO-A:[C-11]去氢骆驼蓬碱、[C-11]氯吉兰和[C-11]贝伐他汀; MAO-B:[C-11]丙炔苯丙胺-D2)的正电子发射断层扫描(PET)成像一直在积极进行。然而,目前尚不清楚不同放射性示踪剂的PET结果测量与实际MAO蛋白水平的定量相关性。我们测量了区域分布(n = 38)和发育/衰老变化(21小时至99岁)的两个MAO的定量免疫印迹在尸检正常人脑。在婴儿中,MAO-A比MAO-B更丰富,这是相反的,因为MAO-B水平在1岁之前增加得更快,并且不像MAO-A,保持稳定增加到衰老。在成年人中,区域蛋白水平的两个单胺氧化酶与文献死后数据的单胺氧化酶活性和结合密度呈正相关,成比例。除[C-11]贝伐他汀(结合电位(BP),r = 0.61,P = 0.15)外,文献中结合的局部PET结果指标与MAO蛋白水平之间的相关性良好(P
Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [C-11]harmine, [C-11]clorgyline, and [C-11]befloxatone; MAO-B: [C-11]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n = 38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [C-11]befloxatone (binding potential (BP), r = 0.61, P = 0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P