title: 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.
abstract: 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 24h 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.
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China; Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China; The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Han
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China; School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, PR China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Luo
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.
authors.forename: Bingrui
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agriculture University, Beijing 100193, PR China. Electronic address: shaolinwang@outlook.com.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China. Electronic address: wangjd53@outlook.com.
authors.forename: Jundong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000633:toxicity*; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D052244:Endocrine Disruptors; D051058:Oncogene Protein v-akt; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Akt; Bisphenol A; ERK/CREB/BDNF pathway; Maternal; Object recognition memory