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The impact of a neonicotinoid pesticide on neural functions underlying learning and memory

新烟碱类农药对学习和记忆神经功能的影响

基本信息

批准号：
10646631
负责人：
Megan M Mahoney
金额：
$ 7.52万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
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：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646631
关键词：
Acetylcholine Acute Address Adult Aerosols Affect Affinity Agriculture Animals Behavior Binding Blood Brain Categories Cells Child Chronic Cognition Compensation Consumption Corpus striatum structure Country Development Dose Dust Environment Exposure to Female Fiber Food Hair Hippocampus Human Human Milk Immune Impairment Inflammation Insecta Insecticides Invertebrates Learning Mammals Measures Mediating Memory Metabolic Modeling Motor Mus Mutagenesis Nervous System Neurophysiology - biologic function Nicotine Nicotinic Agonists Nicotinic Receptors North America Oxidative Stress Performance Pesticides Photometry Physiological Processes Plants Population Pregnancy Prevention strategy Proteins Public Health Receptor Up-Regulation Research Rewards Risk Rodent Safety Saliva Sampling Sex Differences Short-Term Memory Signal Pathway Soil Structure Synaptic plasticity System Testing Transcript Urine Vertebrates Virus Water alpha-bungarotoxin receptor anxiety-like behavior behavior test cognitive function desensitization drinking water exposed human population imidacloprid improved in utero mRNA Expression male mature animal negative affect neural neurogenesis neurophysiology neurotransmitter release nicotine exposure novel pregnant prenatal procedural memory protein expression receptor receptor binding receptor expression receptor function receptor upregulation reproductive response sensor spatial memory trait

项目摘要

Neonicotinoids are pesticides used worldwide and humans are ubiquitously exposed to them. They are selective for invertebrate nicotinic acetylcholine receptors (nAchRs) with a low affinity for mammalian ones, a trait that has contributed to their widespread use and assumed safety in mammals. However, an increasing body of evidence in vertebrates indicates developmental and adult exposure to neonicotinoids negatively affects a broad range of physiological processes including immune, reproductive, and metabolic systems. However, relatively little is known about the mechanisms by which neonicotinoid exposure alters learning and memory or perturbs neurophysiological signaling pathways. Learning and memory are fundamental cognitive functions regulated in large part by the hippocampus and striatum of the brain. This is done, in part, through activation of two forms of nAchRs; α2ß4 and α7. The objective of this proposal is to test the global hypothesis that neonicotinoid exposure, gestationally or in adulthood, impairs performance on spatial and procedural memory tasks by perturbing expression of α2ß4 or α7 receptor expression and acetylcholine release. To address this hypothesis, we will treat adult mice, or pregnant dams, with vehicle, or the environmentally relevant doses of 5.7 mg/kg/day and 0.5 mg/kg/day of imidacloprid. Imidacloprid is the most commonly used neonicotinoid and it has been detected in samples from children and adults. Adult and gestationally exposed mice will be tested for spatial memory and reward learning memory (Aim 1). Following behavioral testing, brains from these animals will be isolated and the protein and mRNA expression of α2ß4 or α7 nAchRs and their subunits will be quantified (Aim 2). Lastly, in adult exposed animals, we will use a virus-mediated fluorescent acetylcholine sensor and fiber photometry to measure acetylcholine release targeting the hippocampus while a freely moving animal is engaged in a spatial working task (Aim 3). We predict males will be more sensitive to neonicotinoids than females and thus have a significantly disrupted performance on memory tasks and have a larger increase in nAchR expression in the brain. We also predict that adult exposure will have a larger effect on nAchR expression compared to gestational exposure. Finally, we predict that imidacloprid exposed animals will have a reduction in acetylcholine release in response to a memory task. The results of this novel and comprehensive study will provide a critical identification of possible mechanisms underlying the impact of neonicotinoids on learning and memory.

新烟碱类杀虫剂是世界范围内使用的农药，人类无处不在地接触到它们。