Galea Liisa A M
Program in Neuroscience, Department of Psychology and Brain Research Centre, University of British Columbia, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4.
Brain Res Rev. 2008 Mar;57(2):332-41. doi: 10.1016/j.brainresrev.2007.05.008. Epub 2007 Jun 9.
Gonadal hormones modulate neurogenesis in the dentate gyrus differentially in male and female adult rodents. Neurogenesis is comprised of at least two components: cell proliferation (the production of new cells) and cell survival (the number of new neurons that survive to maturity). Previous studies have found sex differences in the level of cell proliferation in the dentate gyrus only when comparing females in a high estrogen state to males. This review focuses on the effects of acute and chronic levels of estrogens or androgens on hippocampal neurogenesis in the adult male and female rodent. Evidence is also reviewed for the co-localization of androgen receptors and estrogen receptors (ER) with markers for cell proliferation or immature new cell survival. Briefly, evidence suggests that acute estradiol initially enhances and subsequently suppresses cell proliferation in the dentate gyrus of adult female rodents but may have limited effects in male rodents. Both the two known ER subtypes, ERalpha and beta upregulate hippocampal neurogenesis via cell proliferation. Intriguingly, repeated exposure to estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents. However short-term estradiol treatment (5 days) in male meadow voles enhances new cell survival in the dentate gyrus but only when administered during the 'axon extension' phase. Furthermore, evidence is also reviewed showing a difference in response to acute and chronic estradiol treatment in older female rats compared to younger female rats. Recent findings from our laboratory indicate that testosterone and dihydrotestosterone upregulate hippocampal neurogenesis (via cell survival), but not cell proliferation, in adult male rodents. Effects of endogenous fluctuations in gonadal hormones on adult neurogenesis are observed across the seasons in meadow voles and during pregnancy and lactation in the rat dam. Pregnancy and motherhood differentially regulate adult hippocampal neurogenesis in the adult female rodent, with primiparous rats displaying lower levels of hippocampal cell proliferation and survival after parturition. Few studies have compared males and females but existing research suggests a sex difference in the hormonal regulation of hippocampal neurogenesis in the adult. Clearly more work is needed to elucidate the effects of gonadal hormones on neurogenesis in the dentate gyrus of both male and female rodents across the lifespan, especially if we are to use our knowledge of how adult neurogenesis is regulated to develop strategies to repair neuron loss in neurodegenerative diseases.
性腺激素对成年雄性和雌性啮齿动物齿状回神经发生的调节存在差异。神经发生至少由两个部分组成：细胞增殖（新细胞的产生）和细胞存活（存活至成熟的新神经元数量）。以往的研究仅在将处于高雌激素状态的雌性与雄性进行比较时，才发现齿状回中细胞增殖水平存在性别差异。本综述聚焦于成年雄性和雌性啮齿动物中雌激素或雄激素的急性和慢性水平对海马神经发生的影响。同时也对雄激素受体和雌激素受体（ER）与细胞增殖或未成熟新细胞存活标志物共定位的证据进行了综述。简而言之，有证据表明，急性雌二醇最初会增强成年雌性啮齿动物齿状回中的细胞增殖，随后又会抑制该过程，但对雄性啮齿动物的影响可能有限。两种已知的ER亚型，即ERα和ERβ，均通过细胞增殖上调海马神经发生。有趣的是，反复暴露于雌二醇会调节成年雌性而非雄性啮齿动物的海马神经发生和细胞死亡。然而，在雄性草甸田鼠中，短期雌二醇处理（5天）可增强齿状回中的新细胞存活，但仅在“轴突延伸”阶段给药时才会出现这种情况。此外，也有综述证据表明，与年轻雌性大鼠相比，老年雌性大鼠对急性和慢性雌二醇处理的反应存在差异。我们实验室最近的研究结果表明，睾酮和双氢睾酮可上调成年雄性啮齿动物的海马神经发生（通过细胞存活），但不会影响细胞增殖。在草甸田鼠中，可观察到性腺激素内源性波动对成年神经发生的影响贯穿四季；在大鼠母体中，则可观察到其在怀孕和哺乳期的影响。怀孕和母性对成年雌性啮齿动物的成年海马神经发生有不同的调节作用，初产大鼠在分娩后海马细胞增殖和存活水平较低。很少有研究对雄性和雌性进行比较，但现有研究表明，成年海马神经发生的激素调节存在性别差异。显然，需要开展更多工作来阐明性腺激素在整个生命周期中对雄性和雌性啮齿动物齿状回神经发生的影响，特别是如果我们要利用对成年神经发生调节方式的了解来制定修复神经退行性疾病中神经元损失的策略。
