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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 enhances contextual fear memory and affects the serotoninergic system in juvenile female mice.

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Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.


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.

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