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

• 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
• 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

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.

项目摘要 我们的目标是了解环境污染物，即草甘膦， 焦虑和恐惧相关的行为，并确定肠道微生物之间可能的联系， 失衡和行为缺陷。人类接触化学品的风险增加， 食品防腐剂、农业和工业生产表明， 环境毒素，如草甘膦，以及神经和情感的发展 紊乱草甘膦是草甘膦除草剂中的活性成分， 它被认为对哺乳动物是安全的，因为它通过抑制代谢途径发挥作用， 存在于哺乳动物中。甘氨酸靶向一种仅在植物和微生物中发现的酶。 然而，肠道微生物群通过充当针对病原体的防御而有益于宿主， 调节正常的大脑功能肠脑轴是一个双向沟通， 肠道微生物群和神经系统，包括神经，内分泌和炎症 微生物介导的机制。肠-脑-轴沿着的紊乱可能导致 通过改变微生物群组成和产生级联事件的神经发病机制 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。本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学联系。我们的核心假设是草甘膦可以影响 通过对抗肠道微生物来改善精神健康。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一可能的作用， 焦虑和恐惧的化学物质我们将给受草甘膦污染的饮用水， 过滤水给成年雄性和雌性大鼠，并进行焦虑样和 与恐惧有关的行为。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，我们将确定微生物失衡 这可能与情绪发展过程中大脑病理生理学的变化有关。 紊乱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、脑组织学和肠道微生物群。目标2：确定 草甘膦对恐惧记忆、脑组织学和肠道微生物群的影响。