Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
PLoS One. 2012;7(4):e35901. doi: 10.1371/journal.pone.0035901. Epub 2012 Apr 25.
Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug--fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy.
几种不同的干预措施可以改善抑郁情绪，包括药物和环境因素，如定期体育锻炼。这些效果的分子途径仍不完全清楚。在这项研究中，我们试图确定抗抑郁干预措施的共同机制。我们研究了三组小鼠：用广泛使用的抗抑郁药氟西汀治疗的小鼠、进行自愿运动的小鼠和生活在丰富环境中的小鼠。在分子和细胞水平上研究了接受治疗的小鼠的海马体。接受氟西汀治疗和每天运动的小鼠不仅表现出相似的抗抑郁行为，而且其基因表达和海马神经元也发生了相似的变化。在环境丰富的小鼠中没有观察到这些变化。在氟西汀治疗和自愿运动四周后，观察到神经发生和树突棘密度增加。加权基因共表达网络分析显示，与抗抑郁作用相关的四个不同的共表达基因模块。该网络分析使我们能够识别参与氟西汀和运动作用的分子途径的基因。抗抑郁药物和运动共有的神经元和基因表达变化表明，它们的作用存在共同的机制。对这些发现的进一步研究可以用于揭示抑郁的分子机制，并确定新的治疗途径。
