Molecular & Behavioral Effects of Low Level Mn Exposure

分子

基本信息

批准号：
7676600
负责人：
Tomas R Guilarte
金额：
$ 16.32万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7676600
关键词：
Affect Amphetamines Amyloid Animals Area Arts Attention Automobiles Basal Ganglia Behavior Behavior assessment Behavioral Brain Brain Chemistry Brain region Cellular Stress Response Chromosome Pairing Chronic Cognitive Cognitive deficits Collaborations Corpus striatum structure DRD2 gene Data Diffuse Diffusion Magnetic Resonance Imaging Disease Dopamine Dopamine Receptor Dose Environment Evaluation Evolution Exposure to Functional disorder Funding Future Gasoline General Population Globus Pallidus Glutamates Goals Guidelines Head Health Health Policy Human Image Imaging Techniques Impaired cognition Impairment Knowledge Learning Life Link Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manganese Measures Medial Mediating Memory Metals Modality Molecular Monitor Monkeys Motor Neurobiology Neurologic Neurologic Dysfunctions Neurons Neurosciences Occupational Output Parietal Lobe Pathology Play Population Positron-Emission Tomography Progress Reports Psyche structure Public Health Research Design Resolution Role Sampling Schizophrenia Scientist Source Structure Structure of subthalamic nucleus Synapses System Temporal Lobe Testing Time Toxic Environmental Substances Toxin United States National Institutes of Health Work age related aging brain anthropogenesis base behavior test dopamine transporter executive function frontal lobe improved in vivo molecular imaging nervous system disorder neurobehavioral neurochemistry neuroimaging neuropathology neurotoxicity neurotoxicology neurotransmission nonhuman primate novel processing speed putamen radioligand tool vigilance visual learning white matter

项目摘要

Project Summary: Manganese (Mn) is an essential metal for human health, but exposure to excess levels can cause neurological disease. Emerging evidence suggests that long-term exposures to low levels of anthropogenic or environmental sources of Mn may have detrimental effects on human neurological health. Automobile combustion of gasoline containing methylcyclopentadienyl manganese tricarbonyl (MMT) has the potential to significantly increase Mn exposures to human populations where this fuel additive is used. However, there is a paucity of knowledge on the neurological health effects of chronic exposures to low-levels of Mn. While moderate to high levels of Mn exposure are associated with motor abnormalities and cognitive dysfunction as well as basal ganglia dopaminergic dysfunction in humans and non-human primates. The extent to which lower levels of Mn exposure may target specific cognitive domains and alter brain chemistry is not known. The studies described in this application are the result of a unique and productive on-going collaboration of scientists with expertise in behavioral neuroscience, molecular imaging, molecular and cellular neuroscience, neurotoxicology, neurochemistry and neuropathology applying the latest state-of-the-art behavioral and neuroimaging modalities to understand the behavioral dysfunction and underlying molecular and cellular mechanisms of Mn-induced neurological disease in the living non-human primate brain. Our most recent evidence suggests that chronic Mn exposure in non-human primates produces in vivo neurochemical changes resembling those in schizophrenia. Further, exposure to Mn produces a cellular stress response and diffuse amyloid-¿ plaques in the frontal cortex resembling those in the aging brain and in Alzheimer¿s disease. These preliminary findings provide a putative link of an environmental toxicant (Mn) to mental and neurological disease. The proposed studies will expand on these findings and provide the most comprehensive assessment to date on the neurological consequences of chronic Mn exposure on the non-human primate brain. The knowledge gained will help set future public health policies and guidelines to limit Mn exposures in occupational settings and to the general population. Relevance: The work that we describe in this proposal will define the behavioral, in vivo neurochemistry and neuropathological effects of chronic low level Mn exposure in non-human primates. They represent the most comprehensive assessment to date on the neurological consequences of chronic exposure to levels of Mn that segments of the population are likely to encounter in their environment. The knowledge gained will help set future public health policies and guidelines to limit Mn exposures in occupational settings and to the general population.

项目摘要：锰（MN）是人类健康的必不可少的金属，但是暴露于多余的水平可以引起神经疾病。新兴证据表明，长期暴露于低水平 MN的人为或环境来源可能对人类神经健康有害。含汽油的汽车组合，含有甲基环丙烯二烯基三卡酮（MMT）具有在使用这种燃料添加剂的情况下，可能会显着增加对人类种群的MN暴露的潜力。但是，关于慢性暴露于低水平的神经系统健康影响的知识很少 Mn。虽然中度至高水平的MN暴露与运动异常和认知有关功能障碍以及人类和非人类隐私的基础神经节多巴胺能功能障碍。程度较低水平的MN暴露可能针对特定的认知领域，而改变脑化学不是已知。本应用中描述的研究是独特而有效的持续的结果科学家在行为神经科学，分子成像，分子和细胞方面具有专业知识的合作神经科学，神经毒理学，神经化学和神经病理学应用最新的最新技术行为和神经影像学方式，以了解行为功能障碍和潜在的分子 MN诱导的非人类素数中MN诱导的神经系统疾病的细胞机制。我们最大的最近的证据表明，非人类隐私的慢性MN暴露会产生体内神经化学变化类似于精神分裂症的变化。此外，暴露于MN会产生细胞应力反应，并额叶皮质中的弥漫性淀粉样蛋白斑，类似于大脑衰老和阿尔茨海默氏病中的斑块。这些初步发现提供了环境毒物（MN）与心理和神经系统的推定联系疾病。拟议的研究将扩大这些发现，并提供最全面的评估迄今为止，慢性MN暴露于非人类素数大脑的神经系统后果。获得的知识将有助于制定未来的公共卫生政策和准则，以限制MN暴露占据环境和普通人群。相关性：我们在本提案中描述的工作将定义行为，体内神经化学和慢性低水平MN暴露在非人类隐私中的神经病理学作用。他们代表最大的迄今为止对长期暴露于Mn水平的神经系统后果的全面评估人口的细分市场可能在其环境中遇到。获得的知识将有助于设定未来的公共卫生政策和准则，以限制在占领环境中的MN暴露人口。