Petersén Asa, Wörtwein Gitta, Gruber Susanne H M, Mathé Aleksander A
Translational Neuroendocrine Research Unit, BMC D11, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Neurosci Lett. 2008 May 16;436(3):305-8. doi: 10.1016/j.neulet.2008.03.035. Epub 2008 Mar 19.
Hippocampal neurogenesis is potentially implicated in etiology of depression and as the final common mechanism underlying antidepressant treatments. However, decreased neurogenesis has not been demonstrated in depressed patients and, in animals, reduced cytogenesis was shown in healthy rats exposed to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult cytogenesis. The results also point to the importance of using a disease model and not healthy animals for testing effects of potential treatments for human depression and suggest other cellular mechanisms of action than those that had previously been proposed for escitalopram.
海马神经发生可能与抑郁症的病因有关，并作为抗抑郁治疗的最终共同机制。然而，抑郁症患者中尚未证实神经发生减少，在动物中，暴露于应激源的健康大鼠显示细胞生成减少，但迄今为止，在抑郁症模型中尚未发现。在这里，我们报告，与对照FRL相比，抑郁症大鼠模型弗林德斯敏感系（FSL）海马中BrdU阳性细胞的数量（1）显著更高，（2）母婴分离后FSL和FRL中的数量均增加，（3）在母婴分离的动物中，艾司西酞普兰治疗使其数量减少至未分离动物中的水平。这些结果与普遍的假设相悖，即抑郁症中成年细胞生成减少，抗抑郁治疗的共同机制是增加成年细胞生成。结果还指出了使用疾病模型而非健康动物来测试潜在治疗对人类抑郁症影响的重要性，并提示了与先前提出的艾司西酞普兰作用机制不同的其他细胞作用机制。
