MOUSE MODEL OF MATERNAL IMMUNE ACTIVATION

母体免疫激活(MIA)是由怀孕期间病毒感染引起的，是最具特点的 精神分裂症的非遗传危险因素。我们和其他人开发了一种MIA的小鼠模型 会产生类似精神分裂症的神经生物学和行为缺陷。MIA模型， 与中心的其他动物模型不同，它没有对阿尔法的角色做出任何假设？尼古丁 乙酰胆碱受体。因此，这是一个很好的模型来测试围产期胆碱对 确定这种干预在没有预先假设阿尔法减少的模型中是否有效？尼古丁 感受器。MIA通常被假设与精神分裂症的遗传风险相互作用，因此其最显著的 这种影响发生在遗传脆弱的个体身上。因此，在第二个目标中，我们将测试它的效果 在水坝和胎儿中，谁是克莱纳杂合子的增强？零突变。我们假设 可能存在胎儿基因和MIA损伤的相加效应。此外，大坝的基因型可能是 在监管MIA方面有影响力，因为阿尔法？尼古丁受体已被证明在 炎症反应的缓和。 因此，项目6为该中心引入了一种新的模式，这将影响项目2的S对 婴幼儿感觉门控异常的可能母体原因及S项目1的调查 哪些成年患者对尼古丁激动剂治疗有反应。项目6将获得基因分析支持 来自项目3，来自项目4的表型支持，并将评估项目中人化动物的MIA 5. 相关性(请参阅说明)： 精神分裂症需要新的治疗策略来改善认知功能障碍和负性 并能预防精神病的发展。该中心研究一种烟碱型乙酰胆碱 受体作为新的治疗靶点。研究结果被用来设计一种新的药物治疗方法 精神分裂症和婴儿发育期间的预防性营养干预，两者都激活了这一 Rpr.pntnr

Maternal Immune Activation (MIA) results from viral infection during pregnancy and is the best characterized non-genetic risk factor for schizophrenia. We and others have developed a mouse model of MIA that produces neurobiological and behavioral deficits that resemble those of schizophrenia. The MIA model, unlike the Center's other animal modes, makes no suppositions about the role of alpha? nicotinic acetylcholine receptors. Therefore, it is an excellent model to test the effects of perinatal choline to determine if this intervention is effective in a model that does not pre-suppose diminished alpha? nicotinic receptors. MIA is often hypothesized to interact with genetic risk for schizophrenia, so that its most marked effects are in genetically vulnerable individuals. Therefore, in a second aim, we will test whether its effects are enhanced in dams and fetuses who are heterozygous for the Chrna? null mutation. We hypothesize that there may be additive effects of fetal genotype and the MIA insult. In addition, the dam's genotype may be influential in regulating MIA, because alpha? nicotinic receptors have been shown to play a role in the moderation of inflammatory responses. Project 6 thus introduces a new model to the Center, which will influence Project 2's clinical research on the possible maternal causes of sensory gating abnormalities in infants, as well as Project 1's investigation of which adult patients respond to nicotinic agonist therapies. Project 6 will receive genetic analysis support from Project 3, phenotyping support from Project 4, and will assess MIA in humanized animals of Project 5. RELEVANCE (See instructions): New therapeutic strategies for schizophrenia are needed to improve cognitive dysfunction and negative symptoms and to prevent the development of psychosis. The Center investigates a nicotinic acetylcholine receptor as a new therapeutic target. Investigational results are used to design a new drug treatment for schizophrenia and a preventative nutrient intervention during infant development, both of which activate this rpr.pntnr