MOUSE MODEL OF MATERNAL IMMUNE ACTIVATION

母体免疫激活的小鼠模型

• 批准号: 8120340
• 负责人: ROBERT R FREEDMAN
• 金额: $ 17.5万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8120340
• 关键词: Adult; Animals; Behavioral; Choline; Clinical Research; Development; Fetus; Genetic Risk; Genotype; Impaired cognition; Individual; Infant; Infant Development; Inflammatory Response; Influentials; Instruction; Intervention; Investigation; Modeling; Neurobiology; Nicotinic Agonists; Nicotinic Receptors; Nutrient; Patients; Perinatal; Pharmaceutical Preparations; Phenotype; Play; Pregnancy; Psychotic Disorders; Role; Schizophrenia; Symptoms; Testing; Virus Diseases; design; fetal; genetic analysis; genetic risk factor; immune activation; improved; mouse model; new therapeutic target; non-genetic; novel therapeutics; null mutation; prevent; sensory gating

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

母体免疫激活（MIA）是由怀孕期间病毒感染引起的，是最好的特征 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 小鼠模型 产生类似于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式不同，没有对阿尔法的角色做出任何假设？烟 乙酰胆碱受体。因此，它是测试围产期胆碱对胎儿的影响的一个很好的模型。 确定这种干预措施在不预先假设 alpha 减少的模型中是否有效？烟 受体。人们经常假设 MIA 与精神分裂症的遗传风险相互作用，因此其最显着的特征是 影响发生在遗传易受影响的个体中。因此，在第二个目标中，我们将测试其效果是否 Chrna 杂合子的母鼠和胎儿是否得到增强？无效突变。我们假设 胎儿基因型和 MIA 损伤可能会产生累加效应。此外，母亲的基因型可能是 对调节 MIA 有影响，因为 alpha?烟碱受体已被证明在 调节炎症反应。 项目6为中心引入了一种新的模式，这将影响项目2的临床研究 婴儿感觉门控异常的可能母体原因，以及项目 1 的调查 成年患者对烟碱激动剂疗法有反应。项目6将获得遗传分析支持 来自项目 3，来自项目 4 的表型支持，并将评估项目人源化动物中的 MIA 5. 相关性（参见说明）： 精神分裂症需要新的治疗策略来改善认知功能障碍和消极情绪 症状并防止精神病的发展。该中心研究烟碱乙酰胆碱 受体作为新的治疗靶点。研究结果用于设计新的药物治疗方法 精神分裂症和婴儿发育期间的预防性营养干预，两者都会激活这种 rpr.pntnr