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

项目摘要 我们的目标是了解环境污染物，即草甘膦对 焦虑样行为和恐惧相关行为，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，原因是 食品防腐剂、农业和工业生产表明，接触 环境毒素，如草甘膦，以及神经和情绪的发展 精神错乱。草甘膦是以草甘膦为基础的除草剂的有效成分，最初是 被认为对哺乳动物是安全的，因为它通过抑制一条不是 存在于哺乳动物中。草甘膦的靶标是一种仅存在于植物和微生物中的酶。 然而，肠道微生物区系对宿主有利，因为它起到防御病原体和 调节正常的大脑功能。肠轴-脑轴是一种双向的沟通方式， 肠道微生物区系和神经系统，包括神经、内分泌和炎症 由微生物介导的机制。肠道-脑轴的紊乱可能会导致 改变微生物区系组成和产生一系列事件的神经发病机制 这会导致情绪失调。草甘膦对类焦虑和恐惧的影响- 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、恐惧和肠道微生物区系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可以影响 通过对抗肠道微生物来保持心理健康。了解草甘膦对大鼠肠道的影响 共生菌、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 化学物质会导致焦虑和恐惧。我们要么给受草甘膦污染的饮用水，要么 给成年雄性和雌性大鼠过滤水，并对焦虑样和 与恐惧相关的行为。我们假设长期饮用受草甘膦污染的 水会导致类似焦虑和恐惧的行为增加。此外，通过评估 胃肠道微生物区系组成的变化，我们将识别微生物失衡 这可能与情绪发育过程中大脑病理生理的变化有关。 精神错乱。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，和肠道微生物区系。目标2：确定 草甘膦对恐惧记忆、脑组织学和肠道微生物区系的影响。

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.