Cowen Daniel S, Takase Luiz F, Fornal Casimir A, Jacobs Barry L
Department of Psychiatry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Brain Res. 2008 Sep 4;1228:14-9. doi: 10.1016/j.brainres.2008.06.059. Epub 2008 Jun 24.
There has been ongoing controversy as to whether selective serotonin reuptake inhibitors (SSRIs) exhibit the same antidepressant efficacy and risk profile within different age groups. Although the etiology of such potential differences is currently not clear, age-dependent differences in the rate of hippocampal neurogenesis offer one possibility. In the current studies we have therefore examined whether fluoxetine, the prototypical selective serotonin reuptake inhibitor, differentially modulates neurogenesis in adolescent, young adult, and aged rats. Proliferation in the dentate gyrus was measured by assaying expression of the endogenous proliferative marker, Ki67. Survival of proliferating cells was assayed by staining with BrdU. We confirmed previous reports that the rate of neurogenesis, as well as the survival of proliferating cells, decreases significantly with age. Moderate decreases were found in young adult rats relative to adolescent rats, and profound decreases were found in aged rats. We additionally found that age did not alter the response to 25 days of treatment with fluoxetine. In fact, we did not observe enhancement of hippocampal neurogenesis, nor enhancement of proliferating cell survival, in any of the three age groups despite using doses of fluoxetine which have been reported to be effective. In addition to finding no age-dependent effects, our data question the general reproducibility of previously reported fluoxetine effects in animals.
关于选择性5-羟色胺再摄取抑制剂（SSRI）在不同年龄组中是否具有相同的抗抑郁疗效和风险特征，一直存在争议。尽管目前尚不清楚这种潜在差异的病因，但海马神经发生速率的年龄依赖性差异提供了一种可能性。因此，在当前的研究中，我们研究了典型的选择性5-羟色胺再摄取抑制剂氟西汀是否对青春期、成年早期和老年大鼠的神经发生有不同的调节作用。通过检测内源性增殖标记物Ki67的表达来测量齿状回中的增殖情况。用BrdU染色来检测增殖细胞的存活情况。我们证实了之前的报道，即神经发生速率以及增殖细胞的存活率会随着年龄的增长而显著下降。相对于青春期大鼠，成年早期大鼠有适度下降，而老年大鼠则有显著下降。我们还发现年龄并未改变对氟西汀25天治疗的反应。事实上，尽管使用了据报道有效的氟西汀剂量，但在三个年龄组中的任何一组中，我们都未观察到海马神经发生的增强，也未观察到增殖细胞存活的增强。除了未发现年龄依赖性效应外，我们的数据还对先前报道的氟西汀在动物中的效应的普遍可重复性提出了质疑。
