Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Horm Behav. 2013 May;63(5):709-16. doi: 10.1016/j.yhbeh.2013.03.016. Epub 2013 Apr 6.
Perinatal exposure to bisphenol A (BPA), an endocrine-disrupting chemical, affects the central nervous system, including effects on emotional responses and neurotransmitter release. In this study, we investigated the effects of BPA (250 ng/kg/day, from gestational day 10 to postnatal day 20) on fear memory and serotonin (5-HT) metabolites in the brain using contextual fear conditioning (FC) and high-performance liquid chromatography (HPLC), respectively, in adult and juvenile mice of both sexes. Furthermore, we studied the effects of BPA on the gene expression of 5-HT metabolite-related enzymes and 5-HT receptors using quantitative real-time RT PCR in the brains of juvenile females. BPA enhanced fear memory and increased serotonin metabolite (5-HIAA) levels and 5-HIAA/5-HT in the hippocampus, the striatum, the midbrain, the pons, and the medulla oblongata of juvenile female mice. In contrast, alterations in those areas were much smaller in adult females and in both juvenile and adult males. Furthermore, BPA induced increases in the expression levels of Tph2, Slc6a4, and Maoa mRNA in the hippocampus of juvenile females, indicating that BPA induces hyper 5-HT turnover in the hippocampus. Our results suggest that perinatal exposure to a low dose of BPA enhances fear memory and the 5-HTergic system in juvenile mice.
围产期接触双酚 A（BPA），一种内分泌干扰化学物质，会影响中枢神经系统，包括对情绪反应和神经递质释放的影响。在这项研究中，我们使用情景性恐惧条件反射（FC）和高效液相色谱法（HPLC），分别研究了 BPA（从妊娠第 10 天到出生后第 20 天，每天 250ng/kg）对成年和幼年雌雄小鼠的恐惧记忆和脑内 5-羟色胺（5-HT）代谢物的影响。此外，我们使用定量实时 RT-PCR 研究了 BPA 对幼年雌性小鼠脑中与 5-HT 代谢物相关的酶和 5-HT 受体的基因表达的影响。BPA 增强了幼年雌性小鼠的恐惧记忆，增加了海马体、纹状体、中脑、脑桥和延髓中的 5-羟色胺代谢物（5-HIAA）水平和 5-HIAA/5-HT。相比之下，成年雌性和幼年及成年雄性小鼠的这些区域的变化要小得多。此外，BPA 诱导了幼年雌性小鼠海马体中 Tph2、Slc6a4 和 Maoa mRNA 表达水平的增加，表明 BPA 诱导了海马体中 5-HT 周转率的增加。我们的结果表明，围产期接触低剂量的 BPA 会增强幼年小鼠的恐惧记忆和 5-HT 能系统。
