Department of Biology, Middlebury College, McCardell Bicentennial Hall, Middlebury, VT 05753, USA.
Neuroscience. 2011 Nov 10;195:180-90. doi: 10.1016/j.neuroscience.2011.08.034. Epub 2011 Aug 19.
Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2) sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated, and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed, and (4) testosterone/isolated. All rats were injected with 5-bromo-2'-deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating levels of testosterone may buffer against the neurogenesis-impairing effects of isolation, whereas high doses of testosterone do not.
先前的研究表明，睾丸酮可增强成年雄性大鼠齿状回（dentate gyrus）中的神经发生，而社会隔离在某些条件下会导致成年神经发生减少。本研究使用涉及成年雄性大鼠的两项实验，测试了睾丸酮和社会隔离对成年神经发生的联合影响。在这两项实验中，一半的实验对象被成对饲养，另一半则在实验期间（34 天）单独饲养。对于实验 1，实验对象被分为四组（每组 8 只）：（1）假手术/成对饲养组，（2）假手术/隔离组，（3）去势/成对饲养组，和（4）去势/隔离组。去势组的大鼠被双侧去势，假手术组的大鼠被假去势。对于实验 2，所有大鼠均被去势，并使用睾丸酮丙酸酯（0.500 mg/大鼠，15 天）或油载体进行睾丸酮作用的测试。实验对象被分为四组（每组 8 只）：（1）油/成对饲养组，（2）油/隔离组，（3）睾丸酮/成对饲养组，和（4）睾丸酮/隔离组。所有大鼠均注射 5-溴-2'-脱氧尿苷（BrdU，200 mg/kg 体重），并在 16 天的细胞存活期后使用免疫组织化学方法确定神经发生水平。对于实验 1，与完整组相比，去势组的 BrdU 标记细胞沿齿状回颗粒细胞层和颗粒下区（GCL+SGZ）明显减少，这一效应主要归因于去势/隔离组的神经发生水平较低。对于实验 2，与成对饲养组相比，社会隔离导致 GCL+SGZ 内的神经发生显著减少。睾丸酮注射并不能缓冲这种效应，反而倾向于导致神经发生减少。因此，社会隔离降低了海马神经发生，但睾丸酮的作用并不一致。这表明，正常循环的睾丸酮水平可能缓冲隔离对神经发生的损害作用，而高剂量的睾丸酮则没有。
