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伴有和不伴有自杀行为的抑郁症患者前额叶谷氨酸-谷氨酰胺循环及神经元/胶质细胞谷氨酸转运体的变化

Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide.

作者信息

Zhao J, Verwer R W H, van Wamelen D J, Qi X-R, Gao S-F, Lucassen P J, Swaab D F

机构信息

Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

J Psychiatr Res. 2016 Nov;82:8-15. doi: 10.1016/j.jpsychires.2016.06.017. Epub 2016 Jun 29.

DOI:10.1016/j.jpsychires.2016.06.017
PMID:27450072
Abstract

There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neuronal/glial glutamate transporters was determined by qPCR in postmortem prefrontal cortex. The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) were selected from young MDD patients who had committed suicide (MDD-S; n = 17), from MDD patients who died of non-suicide related causes (MDD-NS; n = 7) and from matched control subjects (n = 12). We also compared elderly depressed patients who had not committed suicide (n = 14) with matched control subjects (n = 22). We found that neuronal located components (EAAT3, EAAT4, ASCT1, SNAT1, SNAT2) of the glutamate-glutamine cycle were increased in the ACC while the astroglia located components (EAAT1, EAAT2, GLUL) were decreased in the DLPFC of MDD-S patients. In contrast, most of the components in the cycle were increased in the DLPFC of MDD-NS patients. In conclusion, the glutamate-glutamine cycle - and thus glutamine transmission - is differentially affected in depressed suicide patients and depressed non-suicide patients in an area specific way.

摘要

有迹象表明谷氨酸代谢与抑郁症或自杀有关。谷氨酸-谷氨酰胺循环和神经元/胶质细胞谷氨酸转运体介导谷氨酸和谷氨酰胺的摄取。通过qPCR测定死后前额叶皮质中谷氨酸-谷氨酰胺循环的各种成分以及神经元/胶质细胞谷氨酸转运体的表达。从自杀的年轻重度抑郁症患者(MDD-S;n = 17)、死于非自杀相关原因的重度抑郁症患者(MDD-NS;n = 7)和匹配的对照受试者(n = 12)中选取前扣带回皮质(ACC)和背外侧前额叶皮质(DLPFC)。我们还将未自杀的老年抑郁症患者(n = 14)与匹配的对照受试者(n = 22)进行了比较。我们发现,在MDD-S患者的ACC中,谷氨酸-谷氨酰胺循环中位于神经元的成分(EAAT3、EAAT4、ASCT1、SNAT1、SNAT2)增加,而在DLPFC中位于星形胶质细胞的成分(EAAT1、EAAT2、GLUL)减少。相比之下,MDD-NS患者DLPFC中循环中的大多数成分增加。总之,谷氨酸-谷氨酰胺循环——以及由此的谷氨酰胺传递——在抑郁自杀患者和抑郁非自杀患者中以区域特异性方式受到不同影响。

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