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）是由妊娠期病毒感染引起的， 精神分裂症的非遗传风险因素我们和其他人已经开发了一种MIA的小鼠模型， 产生类似精神分裂症的神经生物学和行为缺陷。MIA模型， 不像中心的其他动物模式，不假设阿尔法的作用？烟碱 乙酰胆碱受体因此，这是一个很好的模型，以测试围产期胆碱的影响， 确定这种干预在不预先假设阿尔法值减小的模型中是否有效？烟碱 受体。MIA通常被假设与精神分裂症的遗传风险相互作用，因此它最显着 影响的是基因脆弱的个体。因此，在第二个目标中，我们将测试其影响是否 在Chrna杂合子的母体和胎儿中增强？无效突变我们假设 胎儿基因型和MIA损伤可能存在累加效应。此外，母亲的基因型可能是 在监管失踪人口方面有影响力因为阿尔法烟碱受体已被证明在 调节炎症反应。 因此，项目6为中心引入了一种新的模式，这将影响项目2在 婴儿感觉门控异常的可能母亲原因，以及项目1对 哪些成年患者对烟碱激动剂治疗有反应。项目6将获得遗传分析支持 来自项目3，表型分析支持来自项目4，并将在项目4的人源化动物中评估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负性 症状并预防精神病的发展。该中心研究了一种烟碱乙酰胆碱 受体作为新的治疗靶点。研究结果用于设计一种新的药物治疗， 精神分裂症和婴儿发育期间的预防性营养干预，这两者都激活了这一点。 rpr.pntnr