Effects of environmental contaminants on anxiety-like and fear behaviors, and gut-microbiota in rodents

环境污染物对啮齿动物焦虑样和恐惧行为以及肠道微生物群的影响

基本信息

批准号：
10816154
负责人：
FILIPA GODOY-VITORINO
金额：
$ 2.06万
依托单位：
UNIVERSITY OF PUERTO RICO MED SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-12 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10816154
关键词：
Adult Affect Agriculture Amygdaloid structure Anxiety Bacteria Behavior Behavioral Biological Brain Brain region Breathing Chemicals Clinical Communication Consumption Darkness Development Dill Disease Dose Emotional disorder Endocrine Environmental Pollutants Environmental Pollution Enzymes Event Exposure to FOS gene Female Food Food Preservatives Freezing Fright Functional disorder Future Goals Gonadal Hormones Grant Health Herbicides Histology Human Inflammatory Knowledge Light Link Mammals Measures Mediating Memory impairment Mental Health Mental disorders Metabolic Microbe Minority Groups Mission Movement National Center for Complementary and Integrative Health National Institute of Environmental Health Sciences National Institute of Mental Health National Institute on Minority Health and Health Disparities Nervous System Neurodevelopmental Disorder Neurologic Neurons Pathogenesis Pathway interactions Plants Prefrontal Cortex Rattus Reporting Research Domain Criteria Resistance Risk Rodent Role Route Sampling Serotonin Sex Differences Structure Structure of terminal stria nuclei of preoptic region Testing Time Toxic Environmental Substances United States Environmental Protection Agency United States Food and Drug Administration United States National Institutes of Health Water anxiety-like behavior arm behavior change behavior test behavioral study brain circuitry comparison control conditioned fear contaminated drinking water contaminated water drinking dysbiosis emotion dysregulation exposed human population fear memory fecal microbiota glyphosate gut microbes gut microbiota gut-brain axis industrial production male microbial based therapy microbiota microorganism neural pathogen preclinical study response sex shikimate symbiont

项目摘要

Project Summary Our goal is to understand the effects of environmental contaminants, namely glyphosate, on anxiety-like and fear-related behaviors, and determine possible links between gut microbial imbalances and behavioral deficits. The increased risk of human exposure to chemicals from food preservatives, agriculture and industrial production suggests a link between exposure to environmental toxins, such as glyphosate, and the development of neurological and emotional disorders. Glyphosate, the active ingredient in glyphosate-based herbicides, was initially considered safe for mammals since it exerts its effect by inhibiting a metabolic route that is not present in mammals. Glyphosate targets an enzyme only found in plants and microorganisms. However, gut microbiota benefits the host by acting as a defense against pathogens and regulating normal brain function. The Gut-Brain axis is a bidirectional communication between gut microbiota and the nervous system involving neural, endocrine, and inflammatory mechanisms mediated by microbes. Disturbances along the Gut-Brain-Axis may contribute to neural pathogenesis by altering microbiota composition and generating a cascade of events which lead to emotional dysregulation. The influence of glyphosate on anxiety-like and fear- related behaviors is unclear. The long-term goal of this project is to better understand the potential relationship between the influence of glyphosate on anxiety, fear and gut microbiota, by examining potential biological links. Our central hypothesis is that glyphosate can impact mental health by acting against gut microbes. Understanding how glyphosate impacts rat gut symbionts, their behavior and brain pathophysiology will help elucidate a possible role of this chemical to anxiety and fear. We will give either glyphosate-contaminated drinking water or filtered water to adult male and female rats and perform behavioral studies for anxiety-like and fear-related behaviors. We hypothesize that prolonged drinking of glyphosate-contaminated water will lead to increased anxiety-like and fear-related behaviors. In addition, by evaluating changes in the composition of gastrointestinal microbiota, we will identify microbial imbalances that may correlate with changes in brain pathophysiology in the development of emotional disorders. Our two specific aims are as follows: Aim 1: Determine the effects of glyphosate on anxiety-like behaviors, brain histology, and gut microbiota. Aim 2: Determine the effects of glyphosate on fear memory, brain histology, and gut microbiota.

项目概要我们的目标是了解环境污染物（即草甘膦）对焦虑样和恐惧相关的行为，并确定肠道微生物之间可能的联系失衡和行为缺陷。人类接触化学物质的风险增加食品防腐剂、农业和工业生产表明接触食品防腐剂之间存在联系环境毒素，如草甘膦，与神经和情绪的发展失调。草甘膦是草甘膦除草剂的活性成分，最初是被认为对哺乳动物是安全的，因为它通过抑制非正常代谢途径来发挥作用存在于哺乳动物中。草甘膦针对的是一种仅存在于植物和微生物中的酶。然而，肠道微生物群可以防御病原体，从而使宿主受益。调节正常的大脑功能。肠脑轴是肠脑之间的双向通信肠道微生物群和涉及神经、内分泌和炎症的神经系统由微生物介导的机制。沿肠脑轴的干扰可能会导致通过改变微生物群组成并产生一系列事件来调节神经发病机制从而导致情绪失调。草甘膦对焦虑和恐惧的影响相关行为尚不清楚。该项目的长期目标是更好地了解草甘膦对焦虑、恐惧和肠道微生物群的影响之间的潜在关系，通过检查潜在的生物联系。我们的中心假设是草甘膦会影响通过对抗肠道微生物来保持心理健康。了解草甘膦如何影响大鼠肠道共生体、它们的行为和大脑病理生理学将有助于阐明这种可能的作用化学物质会导致焦虑和恐惧。我们将提供受草甘膦污染的饮用水或给成年雄性和雌性大鼠过滤水，并进行焦虑样和焦虑样行为的行为研究与恐惧相关的行为。我们假设长期饮用受草甘膦污染的水会导致焦虑和恐惧相关行为的增加。此外，通过评估胃肠道微生物群组成的变化，我们将识别微生物失衡这可能与情绪发展过程中大脑病理生理学的变化有关失调。我们的两个具体目标如下：目标 1：确定草甘膦对焦虑样行为、大脑组织学和肠道微生物群。目标 2：确定效果草甘膦对恐惧记忆、大脑组织学和肠道微生物群的影响。