Ransome Mark I, Turnley Ann M
Neural Regeneration Laboratory, Centre for Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
Hippocampus. 2008;18(10):1034-50. doi: 10.1002/hipo.20463.
Adult hippocampal neurogenesis (AHN) is modulated by a variety of factors through effects on the proliferation-differentiation-survival regulatory axis. We have employed growth hormone receptor knockout (GH-R-/-) and suppressor of cytokine signaling-2 transgenic (SOCS-2 Tg) mice as models of altered GH-signaling to assess their affects on basal and exercised-induced hippocampal neurogenesis. Assessment of proliferation 24-h after 7-days of bromodeoxyuridine (BrdU) labeling with or without voluntary running showed that the density of BrdU(+) cells in the subgranular zone remained unchanged between genotypes in control housing, while running induced significant increases in BrdU-labeled cells in WT, GH-R-/-, and SOCS-2 Tg mice. The proportion of BrdU/doublecortin and BrdU/S100beta cells did not vary between genotype or running conditions at this time-point. Assessment of cell survival 28-days after BrdU labeling showed that SOCS-2 Tg animals had significantly higher BrdU(+) cell densities in the granule cell layer compared to WT and GH-R-/- animals in control housing and after voluntary running. There were no differences in cell survival between WT and GH-R-/- mice with or without running. Mature phenotype analysis showed similar proportions of BrdU/NeuN and BrdU/S100beta in all groups. While SOCS-2 Tg mice had similar social interaction behaviors and sensorimotor gating, they appeared to be less anxious with heightened basal locomotor activity and showed enhanced performance in the Morris watermaze test. Overall, our data indicated that mice over-expressing SOCS-2 showed increased survival of neurons generated during AHN, which correlated with improved performance in a hippocampal-dependent cognitive task. Furthermore, voluntary running increased AHN in WT, SOCS-2 Tg, and serum-IGF-1-deficient GH-R-/- mice.
成体海马神经发生（AHN）通过对增殖-分化-存活调节轴的影响受到多种因素的调节。我们使用生长激素受体敲除（GH-R-/-）和细胞因子信号转导抑制因子2转基因（SOCS-2 Tg）小鼠作为生长激素信号改变的模型，以评估它们对基础和运动诱导的海马神经发生的影响。在用或不用自愿跑步的情况下，对溴脱氧尿苷（BrdU）标记7天后24小时的增殖情况进行评估，结果显示，在对照饲养条件下，各基因型之间颗粒下区BrdU（+）细胞的密度保持不变，而跑步诱导野生型、GH-R-/-和SOCS-2 Tg小鼠中BrdU标记细胞显著增加。在这个时间点，BrdU/双皮质素和BrdU/S100β细胞的比例在基因型或跑步条件之间没有变化。对BrdU标记后28天的细胞存活情况进行评估，结果显示，与对照饲养条件下以及自愿跑步后的野生型和GH-R-/-动物相比，SOCS-2 Tg动物在颗粒细胞层中的BrdU（+）细胞密度显著更高。在有或没有跑步的情况下，野生型和GH-R-/-小鼠之间的细胞存活没有差异。成熟表型分析显示，所有组中BrdU/NeuN和BrdU/S100β的比例相似。虽然SOCS-2 Tg小鼠具有相似的社交互动行为和感觉运动门控，但它们似乎焦虑程度较低，基础运动活动增强，并且在莫里斯水迷宫试验中表现出更好的成绩。总体而言，我们的数据表明，过表达SOCS-2的小鼠在AHN过程中产生的神经元存活率增加，这与海马依赖性认知任务中的表现改善相关。此外，自愿跑步增加了野生型、SOCS-2 Tg和血清IGF-1缺乏的GH-R-/-小鼠的AHN。
