Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.
Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.
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DOI：
10.1038/nm.2886
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发表时间：
2012-09
期刊：
影响因子：
82.9
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Kang, Hyo Jung;Voleti, Bhavya;Hajszan, Tibor;Rajkowska, Grazyna;Stockmeier, Craig A.;Licznerski, Pawel;Lepack, Ashley;Majik, Mahesh S.;Jeong, Lak Shin;Banasr, Mounira;Son, Hyeon;Duman, Ronald S.
先前的成像和尸检研究报告了重度抑郁症（MDD）受试者的脑体积减少，背外侧前额叶皮层（dlPFC，9区）神经元的大小和密度减少。提示抑郁症患者dlPFC内突触数量和功能均减少。然而，没有直接证据表明MDD中的突触丢失，并且尚未确定这些效应背后的基因表达改变。在这里，我们使用微阵列基因分析和电子显微镜体视学揭示了MDD受试者dlPFC中突触功能相关基因的表达减少，突触数量相应减少。我们还确定了一种转录抑制因子，在MDD中增加，并且当在PFC神经元中表达时足以减少突触相关基因的表达，导致棘突和树突的丢失，并在抑郁症的啮齿动物模型中产生抑郁行为。
Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD). These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression.
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DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li N;Lee B;Liu RJ;Banasr M;Dwyer JM;Iwata M;Li XY;Aghajanian G;Duman RS
通讯作者：
Duman RS
影响因子：
10.6
作者：
Hajszan, Tibor;Szigeti-Buck, Klara;Sallam, Nermin L.;Bober, Jeremy;Parducz, Arpad;MacLusky, Neil J.;Leranth, Csaba;Duman, Ronald S.
通讯作者：
Duman, Ronald S.
影响因子：
11
作者：
Kim, S.;Webster, M. J.
通讯作者：
Webster, M. J.
DOI：
10.1073/pnas.0604041103
发表时间：
2006-10-24
影响因子：
11.1
作者：
Johnson, Kirby D.;Kim, Shin-Il;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
DOI：
10.1073/pnas.0911515107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Cole, Steven W.;Arevalo, Jesusa M. G.;Seeman, Teresa E.
通讯作者：
Seeman, Teresa E.