Gestational and lactational exposure to bisphenol-A affects anxiety- and depression-like behaviors in mice

Bisphenol-A (BPA), an environmental endocrine disruptor, has attracted attention because of its adverse effects on the brain and behavioral development. Previous evidence indicates that perinatal exposure to low levels of BPA affects anxiety-like and cognitive behaviors in adult rodents. The present study aims to investigate the changes of anxiety- and depression-like behaviors of perinatally exposed mice in adulthood following the gestational (gestation days 7 to 20) or lactational (postnatal days 1 to 14) exposure to BPA (0.4 or 4 mg/kg/d). The results indicated that both gestational and lactational exposures to BPA increased anxiety and depression-like behavior in mice of both sexes. The females with gestational exposure exhibited an increased anxiety-like state in the four models tested, including the open field, dark-light transition task, mirrored maze, and elevated plus maze tasks. Furthermore, the females with lactational exposure and the males with gestational exposure exhibited an anxiogenic-like behavior in two models, whereas the males with lactational exposure exhibited an anxiogenic-like behavior only in the elevated plus maze test. The results of the forced swim task showed that gestational exposure markedly increased the immobile time in both sexes, and the same effect was induced by lactational exposure only with 4 mg/kg/d BPA. Furthermore, western blot analyses showed that both gestational and lactational exposures inhibited the expression of the AMPA receptor subunit GluR1 in the hippocampus and amygdala in mice of both sexes, whereas the level of the NMDA receptor subunit NR1 was increased in the amygdala following gestational exposure but was reduced in the hippocampus of the females with lactational exposure. These results suggest that both gestational and lactational exposures to BPA increased anxiety- and depression-like behaviors of adult mice of both sexes. In addition gestational exposure exhibited a stronger effect on anxiety-like state in females. The altered levels of AMPA and NMDA receptors in the hippocampus and amygdala may be associated with BPA-induced behavioral changes.