Effects of Mold Exposure on Brain and Behavior

描述(由申请人提供)：在过去的几年里，暴露在被水破坏的建筑物中的霉菌可能会对人类健康产生严重的不利影响。作为一名神经学家，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、疼痛和认知问题的增加，但还没有发表任何动物研究来研究霉菌暴露是如何导致这些问题的。这个试点项目的目标是开始建立一个老鼠模型，以确定霉菌暴露如何影响大脑功能和行为。霉菌暴露会激活一种先天免疫反应。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一样，会引发“疾病行为”。暴露在霉菌中的患者表现出的许多问题，包括学习障碍，与疾病行为的影响是一致的。暴露在霉菌中的患者在由海马体介导的学习任务类型上存在困难。将进行三个实验来确定不同类型的霉菌暴露对疾病行为的影响：C57BI/6小鼠进行一些海马区依赖的认知任务的能力，小胶质细胞的激活，细胞因子和生长因子的免疫反应，细胞凋亡和神经发生。这些变量之间的关系将被确定。确定潜在的生理过程将允许开发更合理的治疗方法来治疗霉菌引起的认知问题，也可能是由激活相同免疫、内分泌和神经机制的其他疾病过程引起的问题。 对我来说，这个试点项目是研究重点的一个重大变化。它的结构是为了提供我所需的指导和培训，以掌握这项研究所需的技术，完成实验，及时发表它们，并获得SC1或同等资金来继续这一研究。

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.