Effects of Mold Exposure on Brain and Behavior

描述（由申请人提供）：在过去的几年里，很明显，在水损坏的建筑物中暴露于霉菌会对人体健康产生严重的不利影响。作为一名神经科学家，我对霉菌暴露对神经和认知功能的影响特别感兴趣。然而，尽管有越来越多的证据表明霉菌暴露会导致焦虑，抑郁，慢性疲劳，疼痛和认知问题增加，但没有动物研究已经发表，研究霉菌暴露如何导致这些问题。这个试点项目的目标是开始建立一个小鼠模型，以确定霉菌暴露如何影响大脑功能和行为。霉菌暴露激活先天免疫反应。我的基本假设是，霉菌引起的先天免疫激活，就像细菌感染引起的免疫激活一样，引发了“疾病行为”。“许多问题，包括学习缺陷，显示由霉菌暴露的患者是一致的疾病行为的影响。暴露于霉菌的患者在海马体介导的学习任务类型方面存在困难。将进行三个实验以确定不同类型的霉菌暴露对疾病行为的影响：在C57 BI/6小鼠的海马中进行许多海马依赖性认知任务的能力、小胶质细胞活化、细胞因子和生长因子免疫反应性、细胞凋亡和神经发生。将确定这些变量之间的关系。确定潜在的生理过程将允许开发更合理的疗法来治疗霉菌引起的认知问题以及可能由激活相同免疫、内分泌和神经机制的其他疾病过程引起的认知问题。 这个试点项目对我来说是研究重点的一个重大变化。它的结构是为我提供所需的指导和培训，以掌握这项研究所需的技术，完成实验，及时发表，并确保SC 1或同等资金继续这一研究路线。

DESCRIPTION (provided by applicant): Over the past few years, it has become clear that exposure to mold in water-damaged buildings can have severe adverse effects on human health. As a neuroscientist, I am particularly interested in the effects of mold exposure on neural and cognitive function. Yet despite mounting evidence that mold exposure causes increased anxiety, depression, chronic fatigue, pain, and cognitive problems, no animal research has been published examining how mold exposure causes these problems. The goal of this pilot project is to begin to establish a mouse model to determine how mold exposure affects brain function and behavior. Mold exposure activates an innate immune response. My basic hypothesis is that Innate immune activation caused by mold, like that caused by bacterial infection, initiates "sickness behavior." Many of the problems, including the learning deficits, shown by mold-exposed patients are concordant with the effects of sickness behavior. Mold-exposed patients have difficulties with the types of learning tasks mediated by the hippocampus. Three experiments will be run to determine the effects of different types of mold exposure on sickness behavior: the ability to do a number of hippocampal-dependent cognitive tasks, microglial activation, cytokine and growth factor immunoreactivity, apoptosis and neurogenesis in the hippocampus of C57BI/6 mice. The relationships between these variables will be determined. Determination of the underlying physiological processes will allow the development of more rational therapies to treat mold- induced cognitive problems and possibly those caused by other disease processes which activate the same immune, endocrine, and neural mechanisms. This pilot project serves as a major change in research focus for me. It is structured to provide the mentoring and training I need to master the techniques needed for this research, complete the experiments, publish them in a timely fashion, and secure SC1 or equivalent funding to continue this line of research.