Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression -: a gene expression study

被引:111
作者
Bergstroem, A. [1 ]
Jayatissa, M. N.
Thykjaer, T.
Wiborg, O.
机构
[1] Aarhus Psychiat Hosp, Ctr Basic Psychiatr Res, Aarhus, Denmark
[2] Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Biochem, Mol Diagnost Lab, DK-8000 Aarhus, Denmark
[3] OWn Res Aps, Sci Pk Skejby, Aarhus, Denmark
关键词
chronic mild stress; stress resilience; antidepressant drug resistance; Microarray; pathway analysis; Escitalopram; hippocampal neurogenesis; apoptotic pathways;
D O I
10.1007/s12031-007-0065-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The current antidepressant drugs are ineffective in 30 to 40% of the treated patients; hence, the pathophysiology of the disease needs to be further elucidated. We used the chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. A fraction of the animals exposed to CMS is resistant to the development of anhedonia; they are CMS resilient. In the CMS-sensitive animals, the induced anhedonic state is reversed in 50% of the animals when treating with escitalopram, whereas the remaining animals are treatment resistant. We used the microarray and the real-time quantitative reverse transcription polymerase chain reaction technique, as well as the ingenuity pathway analysis software to identify the differential gene expression pathways, which are associated with the occurrence of the treatment resistance and the stress-resilient rats. In the hippocampus, we found a significant upregulation of apoptotic pathways in the treatment-resistant animals and significantly increased expression levels of genes involved in hippocampal signaling in the -CMS-resilient rats. We hypoth-esize that sensitivity to the stress-induced anhedonia in rats is correlated with the impairment of hippocampal neurogenesis.
引用
收藏
页码:201 / 215
页数:15
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