Impact of Bisphenol A on neural stem cells and development in the adult brain

双酚 A 对神经干细胞和成人大脑发育的影响

• 批准号: 8536290
• 负责人: HONGJUN SONG
• 金额: $ 19.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-24 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536290
• 关键词: Acute; Address; Adult; Affect; Affective; Area; Behavior; Behavioral; Brain; Cancer Etiology; Cells; Chemicals; Chronic; Cognition; Data; Dental; Development; Dose; Ecosystem; Employee Strikes; Environment; Environmental Exposure; Environmental Pollution; Environmental Risk Factor; Epoxy Resins; Evaluation; Exposure to; Feedback; Food Container; Foundations; Future; Glial Differentiation; Health; Hippocampal Formation; Hippocampus (Brain); In Vitro; Individual; Investigation; Knowledge; Label; Laboratories; Life; Memory; Nature; Neuraxis; Neuronal Differentiation; Neuronal Plasticity; Neurons; Newborn Infant; Paper; Parahippocampal Gyrus; Participant; Pattern; Perinatal Exposure; Physiological; Physiology; Plastics; Play; Population; Production; Property; Quantitative Evaluations; Regulation; Reproductive Health; Research Personnel; Risk; Role; Slice; Stem Cell Development; Stem cells; Surveys; Synapses; Testing; Vertebral column; adult neurogenesis; base; bisphenol A; cell behavior; coping; density; dentate gyrus; environmental chemical; in vivo; mature animal; migration; nerve stem cell; neurogenesis; neuron development; neuronal survival; newborn neuron; novel; relating to nervous system; research study; response; retroviral-mediated; stem cell population; urinary

DESCRIPTION (provided by applicant): Bisphenol A (BPA) is one of the most prevalent manufactured chemicals in the world. An organic compound with estrogenic effects, it is used in the production of plastic composites and epoxy resins that are used to make food containers, dental products, thermal receipt paper, and many other items that we encounter on a daily basis. Because of its pervasive presence in our environment and ecosystem, it is critical that we understand the physiological effects of our incidental contact with BPA. The objective in this proposal is to focus on the mature central nervous system and identify the role of BPA on neural stem cells and neuronal development in the adult brain. One of the most striking examples of adult neural plasticity is the de novo formation of neurons throughout life in the dentate gyrus of the hippocampus. Convergent data suggests that this phenomenon plays a critical role in cognition and the regulation of affective behavior. Many of these functional roles appear to be part of a feedback loop in which environmental factors can alter the levels of adult neurogenesis, which in turn may alter our ability to cope with environmental demands. It is therefore paramount that one identifies the nature and mechanisms underlying the interaction between this form of adult neural plasticity and the environment. One such area in need of systematic investigation is the neural impact of frequently encountered environmental chemicals. To begin to address this gap in knowledge, the focus here is on BPA as an entry point for a rigorous analysis of how a near ubiquitous chemical contaminant may affect the activation and fate choice of neural stem cells and the development of their neuronal progeny. To accomplish this objective, novel quantitative approaches developed and refined in this laboratory will be used to analyze how BPA may regulate stem cell behavior and the properties of newborn neurons in the adult hippocampus. Taking advantage of a recently developed "clonal analysis" approach, both the identifying and quantifying properties of individual stem cells and stem cell populations in the adult brain following systemic exposure to BPA will be tested (Specific Aim 1). Further quantification of the impact of BPA on the developmental trajectory of newborn neurons will be accomplished using retroviral-mediated fluorescent labeling to enable morphological and electrophysiological analyses (Specific Aim 2). The results of these experiments should provide critical new information on the potential health risks of exposure to BPA and its effect on the adult central nervous system.

描述（由申请人提供）：双酚A（BPA）是世界上最常见的化学制品之一。它是一种具有雌激素作用的有机化合物，用于生产塑料复合材料和环氧树脂，用于制造食品容器，牙科产品，热收据纸和我们日常遇到的许多其他物品。由于它在我们的环境和生态系统中无处不在，我们必须了解偶然接触BPA的生理影响。该提案的目的是关注成熟的中枢神经系统，并确定BPA对成人大脑神经干细胞和神经元发育的作用。成人神经可塑性的一个最引人注目的例子是在整个生命过程中在海马齿状回神经元的从头形成。 海马体聚合数据表明，这种现象在认知和情感行为的调节中起着关键作用。这些功能中的许多似乎是反馈回路的一部分，其中环境因素可以改变成人神经发生的水平，这反过来又可能改变我们科普环境需求的能力。因此，至关重要的是，一个确定的性质和机制之间的相互作用，这种形式的成人神经可塑性和环境。其中一个需要系统研究的领域是经常遇到的环境化学品对神经的影响。为了开始解决这一知识缺口，这里的重点是BPA作为一个切入点，严格分析一个几乎无处不在的化学污染物如何影响神经干细胞的激活和命运选择及其神经元后代的发展。为了实现这一目标，本实验室开发和完善的新的定量方法将用于分析BPA如何调节干细胞行为和成年海马体中新生神经元的特性。利用最近开发的“克隆分析”方法，将测试全身暴露于BPA后成人大脑中单个干细胞和干细胞群的识别和定量特性（具体目标1）。BPA对新生神经元发育轨迹的影响的进一步定量将使用逆转录病毒介导的荧光标记来实现，以进行形态学和电生理学分析（具体目标2）。这些实验的结果应该提供关键的新信息，暴露于BPA的潜在健康风险及其对成人中枢神经系统的影响。

项目成果

Cell-autonomous inactivation of the reelin pathway impairs adult neurogenesis in the hippocampus.

reelin 通路的细胞自主失活会损害海马体中的成体神经发生。

• DOI: 10.1523/jneurosci.1857-12.2012
• 发表时间: 2012
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Teixeira,CatiaM;Kron,MichelleM;Masachs,Nuria;Zhang,Helen;Lagace,DianeC;Martinez,Albert;Reillo,Isabel;Duan,Xin;Bosch,Carles;Pujadas,Lluis;Brunso,Lucas;Song,Hongjun;Eisch,AmeliaJ;Borrell,Victor;Howell,BrianW;Parent,JackM
• 通讯作者: Parent,JackM

Reprogram to pluripotency: a new logic and a chemical cocktail.

• DOI: 10.1093/nsr/nwt007
• 发表时间: 2014-03
• 期刊: National science review
• 影响因子: 20.6
• 作者: Song H;Ming GL
• 通讯作者: Ming GL