Dissertation > Excellent graduate degree dissertation topics show

The Effects of Exposure to Bisphenol-a between Adolescence and Early Adulthood on Behaviors in Mice and Its Molecular Mechanism

Author: TianDong
Tutor: XuXiaoHong
School: Zhejiang Normal University
Course: Zoology
Keywords: bisphenol-A behavior synapse interface modification PSD-95 NMDA receptor
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 11
Quote: 0
Read: Download Dissertation

Abstract

Bisphenol-A (BPA), one of the most representative environmental estrogen contaminations in phenolic compounds, is used in carbonic acid polyester packaging materials of food and beverage, resins lining metal cans, dental solid sealing agent. As a kind of estrogen, BPA also has some affinity to estrogen receptor, which can simulate and interfere the normal metabolic and physiological activities of estrogen in the body. Especially in the period of tissue formation and development, BPA poses a serious threat to human health. Many studies have found that perinatal exposure to BPA can affect brain and behavior of the rodents. Early study in my laboratory showed that perinatal BPA exposure can affect many kinds of social behaviors, as well as sex differentiation in mice offspring. Adolescence is the second development peak period of animal body and the behaviors of adolescent animal is regulated by sex hormones, then we speculate whether adolescent exposure to BPA may affect non-reproductive behavior and the sex differentiation of mice.Synaptic plasticity, which includes synapse interface modification and variability of synapse functions, is sensitive to behaviors、environment and medicine. Postsynaptic density-95 (PSD-95) is one of the most representative scaffold proteins in PSD, regulating the synaptic activity by the integration of the signal transduction. Glutamate NMDA receptors are necessary postsynaptic components of all the excitatory synapses, and their expression is affected by endogenous estrogens.This study further analysed the synaptic interface modification, the relations between synaptic protein and NMDAR, the effects of BPA exposure between adolescence and early adulthood on spontaneous activity behavior, exploratory behavior, anxiety behavior, spatial learning and memory behavior, and explored the molecular mechanisms of animal behavior after exposure to BPA.Methods:In this study, we chose 4-week-old male and female ICR mice(weight 18-23g, clean grade). After acclimatization for 1 week, they were orally exposed to BPA dissolved in peanut oil (40,4000μg/kg/day) or only peanut oil as a vehicle control by sex (n=10) at 8 am everyday 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. After the behavioral detections, we decapitated to take the hippocampal tissue samples as required to observe the structural of synapse interface in hippocampus CA1 by transmission electron microscope, pathological changes in CA1 by HE staining, PSD-95 protein expression in CA1 by immunohistochemistry, NMDA receptor NR1 arid NR2B subunit protein expression by western-blot, as well as the weight、serum levels of estrogen or androgen.Quantity one and Image-Pro Plus were used to measured the protien bands and immunohistochemical images, respectively. Finally, SPSS 15.0 software was used to analyse experimental data.Results:The results were showed by M±SE, and analysed by SPSS15.0.1. Compared with the control groups, the weight of male mice decreased significantly (P<0.05) after exposure to BPA (40,400μg/kg/d), so did the female mice which were exposed to BPA with the concentrations of 40μg/kg/d. but the weight decrease of the former was obvious higher than the latter in the same dose of BPA groups (P<0.01). The results of serum hormone levels showed that BPA had no effects on estrogen and androgen in both female and male mice.2. The results from open field showed that there were no differences in male and female mice groups after BPA exposure, but sexual difference of the frequencies of rearing and buttress standing was abolished. The results from elevated plus-maze displayed that BPA significantly decreased or increased the frequency of open arms entrance and stayed time in the open arms in male and female mice, respectively (P<0.05 or P<0.01), while unprotected head dips in the central area of elevated plus-maze were significantly decreased in male (P<0.05 or P<0.01) but increased in female (P<0.01), resulting in abolishment or the reverse of sex difference in exploration and anxiety behavior in adult mice. The results of Morris water maze test showed that exposure to BPA (40μg/kg/d) significantly extended the average escape pathlength of the male (P<0.05), 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, exposure to BPA (40μg/kg/d) markedly shortened the latency to step down 24h after footshock in male mice (P<0.05) but not in the female, thus the sex difference in passive avoidance memory was induced by exposure to BPA.3. Obverse of the structural of synapse interface showed that, exposure to BPA (40,400μg/kg/d) did not affect the synaptic density, but changed the synaptic interface modification. Compared with the same sex control groups, exposure to BPA (40,400μg/kg/d) significantly widened the cleft of synaptic (P<0.05 or P<0.01), thinned the postsynaptic density (P<0.05 or P<0.01), distinctly shortened the length of active zone(P<0.05 or P<0.01), but had no effects on the curvature of synapse interface in male and female mice. Exposure to BPA (40 ug/kg/d) showed significant gender differences (P<0.05), it was wider in female than in male.4. The results of HE staining showed that Exposure to BPA had no effects on pathological changes in hippocampal CA1. but significantly decreased PSD95 protein expression in hippocampal CA1 in both male and female mice (P<0.05 or P<0.01). The further results of NMD A receptor NR1 and NR2B subunit protein expression in hippocampal by western-blot showed that exposure to BPA (40,400μg/kg/d) decreased the expression of NR1 and NR2B subunit protein significantly in male and female mice (P<0.01). Exposure to the concentrations of 40μg/kg/d of BPA had more obvious down-regulation, which not only abolished the sexual difference in NR1, but also reversed the sexual difference in NR2B in normal male and female mice (male<female, P<0.01)Conclusion:BPA had a sex-specific impact on a variety of behaviors in mice after exposed to BPA between adolescence and early adulthood, and interfered the sex differences in adult mice, which may be related to BPA by widening the synaptic cleft, thinning the postsynaptic density, shortening the length of active zone, down- regulating expression of PSD-95、NR1 and NR2B subunit protein.

The Effects of Exposure to Bisphenol-a between Adolescence and Early Adulthood on Behaviors in Mice and Its Molecular Mechanism

Abstract

Related Dissertations