Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan.
Neuroscience. 2010 Aug 11;169(1):223-8. doi: 10.1016/j.neuroscience.2010.04.047. Epub 2010 Apr 28.
An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents. We previously reported that prenatal exposure to diethylstilbestrol (DES) impaired passive avoidance responses and increased levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (pCaMKII) in the hippocampus of mice. In this study, we examined whether an enriched environment affects the behavioral and neurochemical changes induced in mice prenatally exposed to DES. Male DES-exposed mice were placed in a standard or enriched environment at 3 weeks of age and subjected to behavioral testing after 3 weeks of exposure to these environments. Immunoblot analysis and 5-bromodeoxyuridine (BrdU) immunohistochemistry were then performed. In DES-exposed mice reared in an enriched environment, passive avoidance responses were significantly improved compared to those in mice reared in a standard environment. Moreover, the increase in level of pCaMKII in the hippocampus of DES-exposed mice was reversed by rearing in an enriched environment. Numbers of BrdU-positive cells in the dentate gyrus were significantly increased in normal and DES-exposed mice reared in the enriched environment compared to those in mice reared in the standard environment. These findings suggest that rearing in an enriched environment may mitigate the defects in brain function induced by prenatal exposure to endocrine disrupters such as DES.
丰富的环境已知可促进大脑结构的变化，并增强啮齿动物的学习和记忆能力。我们之前报道过，产前暴露于己烯雌酚（DES）会损害小鼠的被动回避反应，并增加海马体中磷酸化钙/钙调蛋白依赖性蛋白激酶 II（pCaMKII）的水平。在这项研究中，我们研究了丰富的环境是否会影响产前暴露于 DES 的小鼠的行为和神经化学变化。在 3 周龄时，将雄性 DES 暴露的小鼠置于标准或丰富的环境中，并在暴露于这些环境 3 周后进行行为测试。然后进行免疫印迹分析和 5-溴脱氧尿苷（BrdU）免疫组织化学染色。在丰富环境中饲养的 DES 暴露的小鼠中，与在标准环境中饲养的小鼠相比，被动回避反应明显改善。此外，丰富环境中饲养可逆转 DES 暴露小鼠海马体中 pCaMKII 水平的升高。与在标准环境中饲养的小鼠相比，在丰富环境中饲养的正常和 DES 暴露的小鼠的齿状回中 BrdU 阳性细胞的数量明显增加。这些发现表明，在丰富的环境中饲养可能会减轻产前暴露于内分泌干扰物（如 DES）引起的大脑功能缺陷。
