Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models.
Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models.
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DOI：
10.1038/mp.2010.119
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发表时间：
2012-01
影响因子：
11
通讯作者：
中科院分区：
文献类型：
--
作者：
抑郁症的病因仍不清楚，但已提出两个主要的致病假说：单胺缺乏和抑郁症的应激假说。我们使用内源性抑郁和慢性应激的动物模型来评估这些假说。内源性抑郁大鼠及其对照品系是由公认的抑郁症(MDD)模型Wistar-京都(WKY)大鼠通过双向选择培育而成。WKY多不动(WMI)亚系在强迫游泳试验(FST)中表现出高不动/绝望样行为，而对照亚系WKY少不动(WLI)在FST中没有表现出抑郁行为。使用布朗·挪威、费舍尔344、刘易斯和WKY等遗传和行为不同品系的大鼠来研究慢性应激反应。动物要么没有应激(NS)，要么暴露在慢性束缚应激(CRS)下。全基因组微阵列分析确定了内源性抑郁症和慢性应激模型的海马区和杏仁核中差异表达的基因。单胺类递质相关基因的表达在两种模型中均无显著差异。此外，很少有基因在WMI与WLI以及CRS与NS的比较中显示出重叠的变化，这强烈表明内源性抑郁行为与慢性应激相关的分子机制之间存在差异。综上所述，这些结果认为，尽管慢性应激可能导致抑郁行为，但其分子基础不同于动物的内源性抑郁，也可能不同于人类的内源性抑郁，这表明需要不同的治疗方法。新的内源性抑郁相关基因和慢性应激反应基因的发现表明，未探索的分子机制可能成为开发新的治疗药物的靶点。
The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar–Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.
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在两个慢性抑郁症模型中，去甲肾上腺素转运蛋白和药理学多样的抗抑郁药的敲除可以防止行为和脑神经营养蛋白改变。
影响因子：
4.7
作者：
Haenisch B;Bilkei-Gorzo A;Caron MG;Bönisch H
通讯作者：
Bönisch H
DOI：
10.1038/npp.2008.172
发表时间：
2009-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.1
作者：
Gomez, F;Lahmame, A;Armario, A
通讯作者：
Armario, A
DOI：
10.1073/pnas.0813216106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
8
作者：
Feng, Z;Jin, S;Levine, AJ
通讯作者：
Levine, AJ