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

孕妇免疫激活（MIA）是由妊娠期病毒感染引起的，并且是最佳特征 精神分裂症的非遗传危险因素。我们和其他人开发了MIA的鼠标模型， 产生类似精神分裂症的神经生物学和行为缺陷。 MIA模型， 与中心的其他动物模式不同，对α的作用没有任何假设？烟 乙酰胆碱受体。因此，这是测试围产期胆碱对的绝佳模型 确定此干预措施是否在不预先支持的α下降的模型中有效？烟 受体。 MIA通常被认为与精神分裂症的遗传风险相互作用，因此它最明显 影响在遗传脆弱的个体中。因此，在第二个目标中，我们将测试它的影响是否 Chrna杂合子的大坝和胎儿中是否有增强？空突变。我们假设这一点 胎儿基因型和MIA侮辱可能会产生加性作用。此外，大坝的基因型可能是 在调节MIA的影响下，因为α？烟碱受体已被证明在 炎症反应的适度。 项目6因此向中心介绍了一个新模型，该模型将影响项目2的临床研究 婴儿的感官门控异常的可能原因，以及项目1的调查 哪些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 从项目3项目中，项目4的表型支持，并将评估项目的人源化动物中的MIA 5。 相关性（请参阅说明）： 需要针对精神分裂症的新治疗策略来改善认知功能障碍和阴性 症状并防止精神病的发展。该中心研究了烟碱乙酰胆碱 受体作为新的治疗靶点。研究结果用于设计一种新药物治疗 精神分裂症和婴儿发育过程中的预防养分干预措施，这两者都激活了这一点 rpr.pntnr