Effects of Fluoride on Behavior in Genetically Diverse Mouse Models

氟化物对遗传多样性小鼠模型行为的影响

基本信息

批准号：
7771391
负责人：
Pamela K Den Besten
金额：
$ 23.18万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7771391
关键词：
A Mouse A/J Mouse Acquired Dental Fluorosis Address Affect Animals Anxiety Applications Grants Behavior Behavioral Brain Brain region Cognitive Collaborations Communities Cross-Over Studies Dental Enamel Development Discipline Dose Ensure Exhibits Female Fluorides Future Gender Genetic Genetic Variation Goals Human Inbred Mouse Ingestion Institutes Institution Investigation Lead Learning Link Locomotion Memory Methods Mouse Strains Mus Nervous system structure Neurologic Neurologic Effect Oral health Physiological Physiology Population Predisposition Prevalence Publishing Relative (related person)Relative Risks Reporting Rodent School Dentistry Serum Social Behavior System Testing Tooth Diseases Tooth structure Toxic effect Water Supply base behavior test cost effective drinking water fluorosis male molecular marker mouse model neurobehavioral neurochemistry public health relevance research study response risk benefit ratio sex

项目摘要

DESCRIPTION (provided by applicant): The controlled addition of fluoride into public water supplies reduces the prevalence of dental disease and has been a cost effective way to deliver fluoride to the community. However, some speculate that fluoride at high levels may be toxic to several physiological systems including the nervous system. In the proposed studies, we will investigate whether ingested fluoride, at physiological levels, causes neurobehavioral effects in mice. Our preliminary studies found that fluoride induced behavioral changes in female A/J mice given 50 ppm fluoride in their drinking water for at least 3 weeks. We will examine the effects of gender, dose and genetic background in the neurobehavioral effects of fluoride. Our specific aims are: 1) To characterize the neurobehavioral responses to fluoride in inbred mice with different susceptibilities to dental fluorosis, and 2) To determine whether fluoride exposure affects learning and memory in mice. Two strains of mice, A/J (enamel fluorosis sensitive), and C57BL/6 (normal fluoride response), including both males and females, will be exposed to different levels of fluoride in drinking water and then analyzed for fluoride-related alterations in behavior. These behavioral tests will investigate sensorimotor deficits, anxiety, locomotion, and hyperexcitability. Brain and serum fluoride levels will be determined, and molecular markers known to be associated with learning and memory will be compared in fluoride treated and control mice. The proposed studies cross over several disciplines and will be addressed by a collaborative effort between the Gladstone Neurological Institute and UCSF School of Dentistry. The broad scientific and collaborative strengths of both institutions will ensure the careful completion of all aspects of these studies. Findings from these experiments will deepen our understanding of fluoride toxicity and will help to direct future human studies in the important goal to continue to assess relative risk/benefit rations of fluoride in specific populations. PUBLIC HEALTH RELEVANCE: Fluoride is important for optimal dental health. However, at higher fluoride concentrations, animal and human studies have suggested neurological effects of fluoride that have been linked to behavioral changes. In this application we will expose mice to fluoride in drinking water that results in physiologically relevant serum fluoride concentrations, to determine the effects of fluoride on behavior relative to dose, sex, and strain of mouse.

描述（由申请人提供）：在公共供水系统中控制添加氟化物可降低牙科疾病的患病率，并且是向社区提供氟化物的一种经济高效的方式。然而，一些人推测，高浓度的氟化物可能对包括神经系统在内的多个生理系统有毒。在拟议的研究中，我们将研究生理水平上摄入的氟化物是否会对小鼠的神经行为产生影响。我们的初步研究发现，在雌性 A/J 小鼠的饮用水中添加 50 ppm 氟化物至少 3 周后，氟化物会引起行为变化。我们将研究性别、剂量和遗传背景对氟化物神经行为影响的影响。我们的具体目标是：1) 表征具有不同氟斑牙易感性的近交小鼠对氟化物的神经行为反应，2) 确定氟化物暴露是否影响小鼠的学习和记忆。两种小鼠品系，A/J（牙釉质氟中毒敏感）和 C57BL/6（正常氟化物反应），包括雄性和雌性，将暴露于饮用水中不同水平的氟化物，然后分析与氟化物相关的变化。行为。这些行为测试将调查感觉运动缺陷、焦虑、运动和过度兴奋。将测定大脑和血清氟化物水平，并在氟化物处理和对照小鼠中比较已知与学习和记忆相关的分子标记。拟议的研究跨越多个学科，将由格拉德斯通神经研究所和加州大学旧金山分校牙科学院之间的合作来解决。两个机构广泛的科学和合作优势将确保仔细完成这些研究的各个方面。这些实验的结果将加深我们对氟化物毒性的理解，并将有助于指导未来的人类研究，以实现继续评估氟化物在特定人群中的相对风险/效益比的重要目标。公众健康相关性：氟化物对于最佳的牙齿健康非常重要。然而，在较高的氟化物浓度下，动物和人类研究表明氟化物对神经系统的影响与行为变化有关。在此应用中，我们将让小鼠接触饮用水中的氟化物，从而产生生理相关的血清氟化物浓度，以确定氟化物对小鼠行为的影响（与剂量、性别和品系相关）。