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，是最典型的