Neurodevelopmental Effects of Perinatal Endotoxin

围产期内毒素对神经发育的影响

基本信息

批准号：
6765173
负责人：
GARY W BOEHM
金额：
$ 10.97万
依托单位：
TEXAS CHRISTIAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-06-23 至 2006-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Research has shown that immune activation outside the brain may produce changes within the brain and alter subsequent behavior, potentially rendering one more susceptible to stress reactivity and mental illness. Among the many behavioral effects of peripheral immune activation is the potential for a negative impact upon learning and memory processes. A particularly important question that has yet to be thoroughly explored is to what extent do immune-mediated inflammatory events during early development lead to long-term changes in behavior? The specific aims of this exploratory/developmental grant are designed to develop a mouse model of perinatal immune activation and long-term consequences of immune activation upon anxiety, activity, and learning behavior. From these initial exploratory studies, a significant body of research may come, in which key developmental windows (i.e., critical periods) during which the brain is particularly sensitive to immune-induced insult, as well as the key proteins involved in such disturbances, may be identified. The specific aims include: 1). Investigating the long-term effects of perinatal endotoxin (derived from the bacterium E. coil) injections in two commonly used inbred mouse strains on well-validated tests of anxiety and locomotor activity, 2). Investigating the developmental effects of perinatal endotoxin in two commonly used mouse strains on well-established tests of spatial and non-spatial learning and memory, 3). Ascertaining that observed effects of perinatal endotoxin on performance in a given learning paradigm are, in fact, effects on learning, as opposed to effects on performance due to other factors (e.g., increased stress reactivity, increased anxiety, decreased motor activity, etc.), 4). Explore limited parameters of dose, developmental timepoint, and strain-related aspects of the behavioral effects of neonatal endotoxin exposure, and 5). Verify and explore the effects of peripheral endotoxin exposure on proinflammatory cytokine (factors induced by endotoxin that promote inflammation) gene expression within the neonatal brain. These studies will enable us to test the hypothesis that inflammatory cytokines induced in brain following immune activation in the periphery may alter the developmental trajectory of mammals exposed to unusual immune activation during important periods of neural development. Ultimately, this work may contribute to our understanding of important new perinatal risk factors.

描述（由申请人提供）：研究表明，大脑外部的免疫激活可能会在大脑内部产生变化并改变后续行为，从而使人们更容易受到压力反应性和精神疾病的影响。外周免疫激活的许多行为影响中，可能对学习和记忆过程产生负面影响。尚未彻底探讨的一个特别重要的问题是，早期发展过程中免疫介导的炎症事件在多大程度上导致行为长期变化？该探索性/发育赠款的具体目的旨在开发出围产期免疫激活的小鼠模型以及免疫激活对焦虑，活动和学习行为的长期后果。从这些最初的探索性研究中，可能会进行大量的研究，其中关键的发育窗口（即关键时期）在此过程中，大脑对免疫诱导的损伤特别敏感，以及可能涉及此类干扰的关键蛋白质。具体目的包括：1）。研究围产期内毒素（源自细菌E.卷轴）对两种常用的近交小鼠菌株的长期作用在焦虑和运动活性的验证测试中的长期作用，2）。研究围产期内毒素在两种常用小鼠菌株中对空间和非空间学习和记忆的良好测试的发育作用，3）。确定观察到的围产期内毒素对给定学习范式中性能的影响实际上是对学习的影响，而不是由于其他因素引起的对性能的影响（例如增加压力反应性，焦虑症的增加，焦虑症，运动活动降低等），4），4）。探索新生儿内毒素暴露的行为效应的有限剂量，发育时间和与应变相关的方面的有限参数，5）。验证和探索周围内毒素暴露对促炎细胞因子（由内毒素诱导的因素促进炎症）基因表达在新生儿大脑内的影响。这些研究将使我们能够检验以下假设：外周的免疫激活后在大脑中诱导的炎症细胞因子可能会改变在神经发育的重要时期暴露于异常免疫激活的哺乳动物的发育轨迹。最终，这项工作可能有助于我们对重要的新围产期危险因素的理解。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The effects of age on lipopolysaccharide-induced cognitive deficits and interleukin-1ýý expression.

年龄对脂多糖诱导的认知缺陷和白介素-1××表达的影响。

DOI：
10.1016/j.bbr.2010.10.036
发表时间：
2011
期刊：
Behavioural brain research
影响因子：
2.7
作者：
Tarr,AndrewJ;McLinden,KristinaA;Kranjac,Dinko;Kohman,RachelA;Amaral,Wellington;Boehm,GaryW
通讯作者：
Boehm,GaryW

Influence of prenatal stress on behavioral, endocrine, and cytokine responses to adulthood bacterial endotoxin exposure.

产前应激对成年期细菌内毒素暴露的行为、内分泌和细胞因子反应的影响。