Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, New York 10027, USA.
Dev Neurobiol. 2012 May;72(5):743-52. doi: 10.1002/dneu.20987.
Pubertal development is marked by significant decreases in cellular proliferation and neurogenesis in the dentate gyrus of the hippocampal formation. Although it is unclear what mediates these developmental changes in the dentate gyrus, gonadal hormones have been implicated in modulating many neurobiological processes during puberty and various parameters of neurogenesis in adulthood. Thus, it is possible that the gradual and sustained increase in gonadal hormones experienced during puberty plays a role in these changes in neurogenesis. In this experiments, we first quantified cellular proliferation and neurogenesis using 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry, respectively, in the dentate gyrus of prepubertal (30 d), midpubertal (45 d), and adult (90 d) male rats. We found the decline in BrdU and DCX cell numbers throughout these ages was coincident with increases in their plasma testosterone levels. We next tested whether exposure to the pubertal rise in gonadal hormones was necessary for this decrease in hippocampal neurogenesis to occur. Thus, we examined cellular proliferation and neurogenesis in intact 30 day (prepubertal) and 60-day-old (late-pubertal) rats, as well as 60-day-old rats that had previously been gonadectomized or sham-gonadectomized at 30 days of age. Although we again found the expected decline in BrdU and DCX cell numbers between 30 and 60 days of age in the intact groups, there were no differences among the 60-day-old animals, regardless of gonadal status. These data indicate that the pubertal-related decline in hippocampal cellular proliferation and neurogenesis is independent of the pubertal change in gonadal hormones.
青春期发育的标志是海马齿状回中的细胞增殖和神经发生显著减少。虽然尚不清楚是什么介导了齿状回中的这些发育变化,但性腺激素已被牵涉到调节青春期的许多神经生物学过程和成年期的各种神经发生参数。因此,青春期期间逐渐和持续增加的性腺激素可能在这些神经发生变化中发挥作用。在本实验中,我们首先使用 5-溴-2'-脱氧尿苷 (BrdU) 和双皮质素 (DCX) 免疫组织化学分别定量了青春期前 (30 d)、中期 (45 d) 和成年 (90 d) 雄性大鼠齿状回中的细胞增殖和神经发生。我们发现,BrdU 和 DCX 细胞数量的减少与血浆睾丸酮水平的升高相一致。接下来,我们测试了暴露于青春期性腺激素升高是否是发生这种海马神经发生减少所必需的。因此,我们检查了完整的 30 天 (青春期前) 和 60 天 (青春期后期) 大鼠以及 30 天之前已经去势或假去势的 60 天大鼠的细胞增殖和神经发生。尽管我们再次在完整组中发现 30 至 60 天之间预期的 BrdU 和 DCX 细胞数量减少,但无论性腺状态如何,60 天龄动物之间没有差异。这些数据表明,与青春期相关的海马细胞增殖和神经发生减少与青春期性腺激素变化无关。