环境雌激素双酚A对成年小鼠学习记忆和突触结构的影响  

The Effects of Environmental Endocrine Disrupter Bisphenol A on Learning-memory and Synaptic Structure of Adult Mice

作　　者：刘幸毅[1] 徐晓虹[1,2] 张勤[1] 张广侠[1] 季佳琳[1] 董芳妮[1] 杨艳玲[1] 

机构地区：[1]浙江师范大学化学与生命科学学院 [2]浙江师范大学心理研究所,浙江金华321004

出　　处：《心理学报》2013年第9期981-992,共12页Acta Psychologica Sinica

基　　金：国家自然科学基金项目(81172627);浙江省自然科学基金重点项目(Z2090955)

摘　　要：双酚A(bisphenol,BPA)是一种广泛存在的环境内分泌干扰物,它可与雌激素受体结合干扰内源性雌激素对中枢神经系统的调控作用。本研究通过将10周龄小鼠灌胃染毒BPA(0.4、4、40 mg/kg/day)3个月,研究长期BPA暴露对成年小鼠记忆行为和突触可塑性的影响。开场行为测试结果表明,BPA(0.4、4、40mg/kg/day)增加雄性的站立次数和理毛频率,BPA(4 mg/kg/day)却显著减少雌鼠的站立次数。水迷宫和被动回避行为模型检测显示,BPA主要损伤雄鼠的空间学习记忆和被动回避记忆。通过制备海马CA1区超薄切片后,电镜观测发现,BPA(0.4、40 mg/kg/day)暴露降低雄鼠海马CA1区突触数密度,缩短雄鼠突触前活性带长度,减小雄鼠突触后致密体(PSD)厚度,增加雄鼠突触间隙宽度。进一步用Western blot方法检测突触前、后的标志性蛋白Synapsin I和PSD95以及兴奋性氨基酸NMDA受体NR1亚基和AMPA受体GluR1亚基蛋白的表达,发现BPA暴露致雄鼠Synapsin Ⅰ、PSD95、NR1蛋白表达水平下调。而BPA对雌鼠的记忆行为、突触形态、突触蛋白和受体蛋白均没有明显作用。以上结果提示长期BPA暴露性别特异性地影响成年小鼠的活动性和探究行为,损伤雄鼠的学习记忆,这些作用可能通过下调突触蛋白和NMDA受体的表达而负性影响突触结构可塑性,最终影响雄鼠的学习记忆功能。Bisphenol A（BPA）,one of the most common environmental endocrine disrupters,can bind to estrogen receptors（ERs） to interfere with the regulation of endogenous estrogen on the central nervous system.The aim of the present study was to investigate the effects of long-term exposure to BPA on the learning and memory behavior.The adult mice at age of 10 weeks were exposed to BPA（0.4,4,and 40 mg/kg/day） or sesame oil for 12 weeks.In open field test,BPA increased the frequencies of rearing and grooming of the males,but reduced the frequency of rearing in the females.Exposure to BPA（0.4 or 40 mg/kg/day） extended the escape pathlength to find the hidden platform in Morris water maze and shortened the step-down latency 24 h after footshock of the males,but no changes were found in the females.Meanwhile,BPA induced a reduced numeric synaptic density and a negative effect on the synaptic structural modification,including the enlarged synaptic cleft and the reduced length of active zone and PSD thickness in the hippocampus of the males.Western blot analyses further indicated that BPA down-regulated the expressions of synaptic proteins（synapsin I and PSD-95） and NMDA receptor subunit NR1 in the hippocampus of the males.These results suggest that long-term exposure to the low levels of BPA in adulthood sex-specifically impaired spatial and passive avoidance memory of mice.These effects may be associated with the higher susceptibility of hippocampal synaptic plasticity processes,such as remodeling of spinal synapses and the expressions of synaptic proteins and NMDA receptor,to BPA in the adult males.After acclimatization for one week,adult male and female ICR mice were orally exposed to BPA dissolved in peanut oil（40,4,0.4 mg/kg/day） or only peanut oil as a vehicle control from 10 weeks of age throughout 22 weeks.At 22 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,an

关 键 词：双酚A 学习记忆 突触形态结构 SYNAPSIN Ⅰ PSD-95 NMDA受体 

分 类 号：B845[哲学宗教—心理学]