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

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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.