成年期双酚A暴露对小鼠行为的影响

Effects of Adulthood Exposure to Bisphenol-A on Behaviors in Mice

探究成年期环境雌激素双酚A(bisphenol A,BPA)暴露对不同性别小鼠行为的影响。出生5周的小鼠灌胃染毒BPA(40、400μg/kg/d),同时设对照组。染毒8周后,以开场行为检测小鼠的自发活动及探究行为,以高架十字迷宫检测小鼠的焦虑和探究行为,以水迷宫检测小鼠的空间学习记忆行为,以跳台检测小鼠的被动回避记忆行为。结果显示,BPA暴露不影响同性别小鼠在开场中的各种行为,但消除了悬空站立和扶壁站立频率的性别差异。高架十字迷宫行为测试中,BPA暴露显著减少雄鼠进入开放臂的次数和停留时间(p<0.05和p<0.01),却显著增加雌鼠进入开放臂的次数和停留时间(p<0.05和p<0.01);同时,BPA暴露显著减少雄鼠(p<0.05和p<0.01)却增加雌鼠在中央区的探头次数(p<0.01),消除甚至反向诱导成年小鼠焦虑行为和探究行为的性别分化。BPA(40μg/kg/d)暴露显著延长成年雄鼠在水迷宫中搜寻平台的平均距离(p<0.05),但对雌鼠没有影响,BPA因此消除了正常成年小鼠空间记忆行为的性别差异。BPA(40μg/kg/d)暴露显著缩短了雄鼠在遭电击24h后跳下平台的潜伏期(p<0.05),但对雌鼠没有明显影响,并因此诱导成年小鼠被动回避行为的性别差异。以上结果表明,成年期BPA暴露可性别特异性地影响小鼠的多种行为,干扰成年小鼠行为的性别差异。

Bisphenol-A （BPA）, one of the well-known environmental endocrine disrupters with estrogen activity is a widely used industrial compound. With its expanded uses, BPA can be seen everywhere around us, and even has become an integral part of our daily life. As a result it makes more and more adult exposure to BPA in daily life. In recent years, many studies have focused on its toxicity to the reproductive system and development, but few studies on the adult brain and behaviors. It is reported that estrogen not only affects the development of the brain, but also participates in the adult brain plasticity and cognitive functions, so it is important to study the effects of adult exposure to BPA on brain. The purpose of the present study is to investigate whether adulthood exposure to BPA affects behaviors in mice. After acclimatization for one week, adult male and female ICR mice were orally exposed to BPA dissolved in peanut oil （40, 400 μg/kg/day） or only peanut oil as a vehicle control from 5 weeks of age throughout 14 and a half weeks of age. At 13 weeks of age, open field, elevated plus-maze, Morris water maze, and step-down were respectively used to test spontaneous activity and exploratory behavior, anxiety, spatial learning and memory, and passive avoidance memory in mice. The results showed that adulthood exposure to BPA for 8 weeks significantly inhibited the growth of body weight of male and female mice （p0.05）. Sexual difference of the frequencies of rearing and buttress standing in open field was abolished by adulthood exposure to BPA. The frequency of open arms entrance, the staying time in the open arms, and unprotected head dips in the central area of elevated plus-maze were significantly decreased in male （p0.05 or p0.01） but were increased in female （p0.05 or p0.01）, resulting in abolishment or reverse of sex difference in exploration and anxiety behavior in adult mice. The results of Morris water maze test showed that adulthood exposure to BPA （40 ？g/kg/d） significantly extended the average escape pathlength of the male （p0.05）, while no marked effect was found in the female, and BPA thus eliminated sex difference of spatial memory in adult mice. In step down test, adulthood exposure to BPA markedly shortened the latency to step down 24 h after footshock in male mice （p0.05） but not in female, and the sex difference in passive avoidance memory was thus induced by exposure to BPA at 40 ？g/kg/d （p0.01）. These results suggest that adulthood exposure to BPA affected multiple behaviors and disturbed the sexual difference of these behaviors in mice.