Evidence of altered polyamine concentrations in cerebral cortex of suicide completers.
Evidence of altered polyamine concentrations in cerebral cortex of suicide completers.
复制标题
DOI：
10.1038/npp.2010.17
复制
发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的研究表明，自杀完成者大脑中多胺相关基因的表达发生了改变，包括多胺催化剂中的关键酶亚精胺/精胺N1-乙酰转移酶（SAT 1）的广泛下调，这表明了试图增加大脑多胺水平的代偿机制。鉴于多胺系统的复杂性，多胺水平的定量是理解基因表达失调的下游效应的重要步骤。我们开发了一种方法，采用高分辨率毛细管气相色谱（GC）结合质谱（MS）用于定量的多胺从死后的脑组织，这使我们能够准确地测量精脒和腐胺浓度在死后的脑组织。使用这种方法，我们分析了腐胺和亚精胺水平，共126个样本从布罗德曼区（BA）4，8/9，和11，从42名受试者，包括16自杀完成者与抑郁症，13非抑郁症自杀完成者，和13名对照组。腐胺和亚精胺水平均在预期的纳摩尔范围内，与对照组相比，有抑郁症史的自杀完成者的大脑中腐胺和亚精胺水平显著升高。这些结果未考虑可能的混杂因素。这是第一个GC-MS研究分析腐胺和亚精胺的表达从死后的脑组织，并证实了先前的研究提出的假设，表明腐胺和亚精胺水平的改变自杀/抑郁症。
Recent studies have implicated alterations in the expression of polyamine-related genes in the brains of suicide completers including widespread downregulation of spermidine/spermine N1-acetyltransferase (SAT1), the key enzyme in polyamine catabolism, suggesting compensatory mechanisms attempting to increase brain levels of polyamines. Given the complexity of the polyamine system, quantification of the levels of the polyamines is an essential step in understanding the downstream effects of dysregulated gene expression. We developed a method employing high-resolution capillary gas chromatography (GC) in combination with mass spectrometry (MS) for quantitation of polyamines from post-mortem brain tissue, which allowed us to accurately measure spermidine and putrescine concentrations in post-mortem brain tissues. Using this method, we analyzed putrescine and spermidine levels in a total of 126 samples from Brodmann areas (BA) 4, 8/9, and 11, from 42 subjects, comprising 16 suicide completers with major depression, 13 non-depressed suicide completers, and 13 control subjects. Both putrescine and spermidine levels fell within the expected nanomolar ranges and were significantly elevated in the brain of suicide completers with a history of major depression as compared to controls. These results were not accounted by possible confounders. This is the first GC-MS study to analyze the expression of putrescine and spermidine from post-mortem brain tissue and confirms the hypothesis raised by previous studies indicating alterations in putrescine and spermidine levels in suicide/major depression.
登录
查看更多内容
DOI：
10.1080/00048670903001943
发表时间：
2009-01-01
影响因子：
4.6
作者：
Bennett, Maxwell
通讯作者：
Bennett, Maxwell
DOI：
10.1016/0020-711x(81)90080-x
发表时间：
1981-01-01
期刊：
INTERNATIONAL JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BOLKENIUS, FN;SEILER, N
通讯作者：
SEILER, N
影响因子：
4.2
作者：
CARLSON, MD;PENNEY, JB;YOUNG, AB
通讯作者：
YOUNG, AB
影响因子：
3.5
作者：
Ferioli, ME;Pinotti, O;Pirona, L
通讯作者：
Pirona, L
DOI：
10.1002/ajmg.b.30901
发表时间：
2009-09-05
影响因子：
2.8
作者：
Guipponi, Michel;Deutsch, Samuel;Malafosse, Alain
通讯作者：
Malafosse, Alain