Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression -: a gene expression study
Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression -: a gene expression study
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DOI：
10.1007/s12031-007-0065-9
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Wiborg, O.
中科院分区：
文献类型：
--
作者：
Bergstroem, A.;Jayatissa, M. N.;Wiborg, O.
目前的抗抑郁药物在30%到40%的治疗患者中无效，因此，疾病的病理生理学需要进一步阐明。我们使用慢性轻度应激(CMS)范式在大鼠中诱发快感缺失，这是严重抑郁症的核心症状。接触CMS的一小部分动物对快感缺乏症的发展具有抵抗力；它们具有CMS的弹性。在对CMS敏感的动物中，用艾司匹兰治疗时，50%的动物被逆转了诱导的无享乐状态，而其余的动物对治疗具有抵抗力。我们使用基因芯片和实时定量逆转录聚合酶链式反应技术，以及独创性通路分析软件，寻找与治疗耐药和应激恢复大鼠相关的差异基因表达通路。在海马区，我们发现耐药动物的凋亡通路显著上调，CMS弹性大鼠海马区信号转导相关基因的表达水平显著增加。我们假设，大鼠对应激性快感缺失的敏感性与海马神经发生的损害有关。
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.