Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus

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• 作者：Chong Wang^a ; ^b ; Zhihui Li^a ; Haijun Han^a ; ^c ; Guangying Luo^a ; ^d ; Bingrui Zhou^a ; Shaolin Wang^e ; ^{shaolinwang@outlook.com" class="auth_mail" title="E-mail the corresponding author} ; Jundong Wang^a ; ^{wangjd53@outlook.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Maternal ; Bisphenol A ; Object recognition memory ; Akt ; ERK/CREB/BDNF pathway
• 刊名：Toxicology
• 出版年：2016
• 出版时间：3 February 2016
• 年：2016
• 卷：341-343
• 期：Complete
• 页码：56-64
• 全文大小：1742 K

文摘

Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9–20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index = the time spent exploring the novel object/(the time spent exploring the novel object + the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24 h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that impairment may be related to a decrease in Akt activation and an inhibition of the ERK/CREB/BDNF pathway in the hippocampus. This study also adds new evidence that suggests BPA has an antagonistic effect on the action of estrogen in the brain.