Environmental Etiologies of Neurological Disorders (NEUROTOXICOLOGY 24)

神经系统疾病的环境病因（神经毒理学 24）

• 批准号: 7408791
• 负责人: Joan Marie Cranmer
• 金额: $ 2.62万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408791
• 关键词: Age; Aging; Animal Disease Models; Animals; Behavior; Biological Markers; Caffeine; Chemical Exposure; Chemicals; Child; Clinical; Clinical Research; Complex; Condition; Detection; Development; Disease; Distant; Environmental Exposure; Environmental Impact; Environmental Risk Factor; Epidemiologic Studies; Etiology; Exhibits; Exposure to; Gender; Genetic; Health; Health protection; Human; Immune; Integration Host Factors; Lead; Methylmercury Compounds; Modeling; Modification; Neurotoxins; Obesity; Onset of illness; Parkinson Disease; Play; Population; Prevention; Public Health; Research; Risk; Risk Factors; Rodent; Sample Size; Sex Characteristics; Smoking; Socioeconomic Status; Staging; Stress; Therapeutic; Therapeutic Intervention; Toxic Environmental Substances; aging gene; environmental chemical exposure; genetic risk factor; human disease; improved; male; nervous system disorder; neurotoxicology; nutrition; young adult

DESCRIPTION (provided by applicant) "Environmental Etiologies of Neurological Disorders: Modifiers of Risk: Genes, Age, Gender, Nutrition, Simultaneous Exposures, Socio-Economic Status". It has become increasingly evident that many human neurological diseases and disorders arise from complex interactions of multiple risk factors, of which environmental chemical exposures may serve as one contributing risk. Other environmental and host factors, such as genetic background, stage of development, dietary status, immune status, obesity, stress, socioeconomic status, gender, aging, behavior, and intercurrent disease state, as well as simultaneous chemical exposures, can also contribute. For example, Parkinson's disease exhibits gender differences, and protection is conferred by caffeine and smoking. The impact of neurotoxicants like lead and methylmercury is heavily influenced by developmental windows, with children showing significantly greater vulnerability. Thus, a full understanding of the true risk posed by any environmental toxicant for human neurological diseases or disorders will ultimately require assessments of its interaction with other relevant environmental, host and genetic risk factors and other modifiers of effect. Despite these complexities, the paradigms used to understand the impact of environmental exposures as risk factors for human diseases continue to rely on approaches that fail to capture this reality. Instead, they focus on exposures to single chemicals in isolation from other risk factors. Animal studies often examine effects of a single chemical in young adult, mostly male rodents, ignoring, for instance, the potential importance of age and gender. Epidemiological and clinical studies generally focus on main effects of environmental exposures, since risk modification, as reflected in statistical interactions, is considered inaccessible because of inadequate sample sizes. Consequently, as models of diseases and disorders, current research approaches are distant from actual human conditions, constraining the ability to determine pathophysiological mechanisms from which biomarkers and therapeutic strategies can be identified, thereby limiting the ability to protect human health. An understanding of the interactions of host and environmental risk factors with environmental chemical exposures in the etiology of neurological diseases and disorders allows the development of increasingly more realistic and valid animal models of disease, and more focused clinical /epidemiological studies. Refined animal and human models will expedite the discovery of pathophysiological mechanisms of environmentally-related diseases and disorders, and thus improve the ability to define biomarkers of disease onset and progression, as well as potential targets for therapeutic interventions, thereby leading to improved prevention and detection strategies. Understanding how risk factors interact is also critical in the context of global public health protection, since different populations and cultures bring different sets of risk factors into play.

描述（由申请人提供） “神经系统疾病的环境病因：风险调节因素：基因、年龄、性别、营养、同时暴露、社会经济状况”。 越来越明显的是，许多人类神经系统疾病和紊乱是由多种危险因素复杂的相互作用引起的，其中环境化学物质暴露可能是其中之一。其他环境和宿主因素，例如遗传背景、发育阶段、饮食状况、免疫状态、肥胖、压力、社会经济地位、性别、衰老、行为和并发疾病状态，以及同时接触的化学物质，也可能有所影响。例如，帕金森病表现出性别差异，咖啡因和吸烟可以提供保护。铅和甲基汞等神经毒物的影响很大程度上受到发育窗口的影响，儿童表现出明显更大的脆弱性。因此，要充分了解任何环境毒物对人类神经系统疾病或紊乱造成的真正风险，最终需要评估其与其他相关环境、宿主和遗传风险因素以及其他效应调节因素的相互作用。 尽管存在这些复杂性，用于理解环境暴露作为人类疾病危险因素的影响的范式仍然依赖于无法捕捉这一现实的方法。相反，他们专注于与其他风险因素隔离的单一化学品的暴露。动物研究经常检查单一化学物质对年轻成年动物（主要是雄性啮齿动物）的影响，而忽略了年龄和性别的潜在重要性等。流行病学和临床研究通常侧重于环境暴露的主要影响，因为统计相互作用中反映的风险修正由于样本量不足而被认为是无法获得的。因此，作为疾病和病症的模型，当前的研究方法与人类的实际状况相距甚远，限制了确定病理生理机制的能力，从而确定生物标志物和治疗策略，从而限制了保护人类健康的能力。 了解宿主和环境风险因素与环境化学暴露在神经系统疾病和紊乱的病因学中的相互作用，可以开发出越来越现实和有效的疾病动物模型，以及更有针对性的临床/流行病学研究。精致的动物和人类模型将加快发现与环境相关的疾病和病症的病理生理机制，从而提高确定疾病发作和进展的生物标志物以及治疗干预的潜在目标的能力，从而改善预防和检测策略。了解风险因素如何相互作用对于全球公共卫生保护也至关重要，因为不同的人群和文化会带来不同的风险因素。