An enriched environment mitigates the brain-disruptive effects of prenatal diethylstilbestrol exposure in mice

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.