Housing in Environmental Complexity Following Wheel Running Augments Survival of Newly Generated Hippocampal Neurons in a Rat Model of Binge Alcohol Exposure During the Third Trimester Equivalent
Housing in Environmental Complexity Following Wheel Running Augments Survival of Newly Generated Hippocampal Neurons in a Rat Model of Binge Alcohol Exposure During the Third Trimester Equivalent
复制标题
DOI：
10.1111/j.1530-0277.2011.01726.x
复制
发表时间：
2012-07-01
影响因子：
3.2
通讯作者：
Klintsova, Anna Y.
中科院分区：
文献类型：
--
作者：
Hamilton, Gillian F.;Boschen, Karen E.;Klintsova, Anna Y.
背景 新生大鼠在大脑生长突增期间暴饮暴食会导致成年大鼠海马齿状回 (DG) 神经发生缺陷。我们实验室先前的数据表明，从出生后第 30 天（PD）开始的 12 天自愿轮跑（WR）显着增加了酒精暴露（AE）和对照大鼠中 PD42 上 DG 中新生成细胞的数量，但 30 天后，WR 的持续有益作用仅在对照大鼠中明显增加。这项研究测试了这样的假设：在 WR 后将大鼠圈养在复杂的环境 (EC) 中会促进 WR 刺激的新生成细胞的存活，特别是在 AE 大鼠中。方法 PD4 至 9 日，对幼犬进行酒精插管（5.25 g/kg/d）、假插管（SI）或正常饲养。在实验 1 中，动物在 PD30 至 42 期间被分配到 WR 或社会饲养 (SH)。在 PD42 上，给动物注射溴脱氧尿苷（BrdU；200 mg/kg）并在 2 小时后灌注，以确认 WR 诱导的增殖刺激。在实验2中，所有动物在PD30至42时接受WR，并在WR的最后一整天注射BrdU。在 PD42 上，动物被随机分配至 EC (WR/EC) 或 SH (WR/SH)，持续 30 天，随后进行灌注，并对大脑进行免疫组织化学染色处理，以识别 DG 中的 BrdU+-、Ki67+- 和 BrdU+/NeuN+ 标记细胞。结果 在实验 1 中，WR 暴露显着增加了所有 3 种出生后条件下的增殖细胞数量。在实验2中，与给予WR/SH的对照大鼠相比，给予WR/SH的AE大鼠的BrdU+细胞显着减少。然而，与相同新生儿治疗的 WR/SH 大鼠相比，WR/EC 经历显着增加了 AE 和 SI 组中存活的 BrdU+ 细胞数量。在各种条件下，DG 中大约 80% 的存活 BrdU+ 细胞均用 NeuN 共同标记。结论 WR 和 EC 可以为开发人类干预措施提供行为模型，以改善与胎儿酒精谱系障碍相关的海马依赖性损伤。
Background Binge-like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus (DG). Previous data from our laboratory demonstrated that 12 days of voluntary wheel running (WR) beginning on postnatal day (PD) 30 significantly increased the number of newly generated cells evident in the DG on PD42 in both alcohol-exposed (AE) and control rats, but 30 days later a sustained beneficial effect of WR was evident only in control rats. This study tested the hypothesis that housing rats in environmental complexity (EC) following WR would promote the survival of the newly generated cells stimulated by WR, particularly in AE rats. Methods On PD4 to 9, pups were intubated with alcohol in a binge-like manner (5.25 g/kg/d), sham-intubated (SI), or reared normally. In Experiment 1, animals were either assigned to WR during PD30 to 42 or socially housed (SH). On PD42, animals were injected with bromodeoxyuridine (BrdU; 200 mg/kg) and perfused 2 hours later to confirm the WR-induced stimulation of proliferation. In Experiment 2, all animals received WR on PD30 to 42 and were injected with BrdU on the last full day of WR. On PD42, animals were randomly assigned either to EC (WR/EC) or to SH (WR/SH) for 30 days and subsequently perfused and brains were processed for immunohistochemical staining to identify BrdU+-, Ki67+-, and BrdU+/NeuN+-labeled cells in DG. Results In Experiment 1, WR exposure significantly increased the number of proliferating cells in all 3 postnatal conditions. In Experiment 2, the AE rats given WR/SH had significantly fewer BrdU+ cells compared with control rats given WR/SH. However, WR/EC experience significantly increased the number of surviving BrdU+ cells in both the AE and SI groups compared with WR/SH rats of the same neonatal treatment. Approximately 80% of the surviving BrdU+ cells in the DG across the conditions were colabeled with NeuN. Conclusions WR followed by EC could provide a behavioral model for developing interventions in humans to ameliorate hippocampal-dependent impairments associated with fetal alcohol spectrum disorders.