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Effects of Complement-lq Immune Activation on Synapse Formation in Schizophrenia

补体-lq 免疫激活对精神分裂症突触形成的影响

基本信息

批准号：
8883715
负责人：
ROBERT H YOLKEN
金额：
$ 14.83万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8883715
关键词：
Affect Animals Antigen-Antibody Complex Antigens Astrocytes Autopsy Basic Science Binding Biological Markers Blood Brain Caseins Clinical Clinical Sciences Collection Complement Complement 1q Complement Activation Complex Dendritic Spines Development Disease Exposure to Gene Expression Genes Glean Human Humoral Immunities Immune Response Genes Immune response Individual Infection Interneurons Left Location Measures Microglia Modeling Molecular Profiling Mutant Strains Mice Neurons Oligodendroglia Penetration Peripheral Peripheral Blood Mononuclear Cell Permeability Sampling Schizophrenia Serum Staging Synapses Testing Tight Junctions Toxoplasma gondii Toxoplasmosis Vertebral column case control complement system density design food antigen frontal lobe gamma-Aminobutyric Acid gene environment interaction immune activation mutant postnatal synaptogenesis

项目摘要

Individuals with schizophrenia have increased humoral immunity to infectious and food antigens. Increased complement activation and increased levels of circulating immune complexes (CIC) are found in individuals with this disease. The complement factor C1q that binds these complexes is also highly expressed at synaptic locations in the developing cortex. Project 6 will test the hypothesis that DISC1 mutant mice display increased C1q activation in the brain. Furthermore, we predict that early postnatal exposure to an environmental trigger such as Toxoplasma gondii infection will further exacerbate C1q activation in the brain of DISC1 mutant mice to contribute to GABA interneuron and spine density deficits in the developing frontal cortex. Extensive case-controlled collections of blood and CSF taken at various stages of disease in conjunction with matched post-mortem serum and frontal cortex samples will allow parallel studies of human samples with DISC1 mutant mice. Specific Aim 1 will test the hypothesis that following penetration of a model antigen, casein, through the GI barrier, C1q-associated immune complexes are formed, leaving molecular signatures in human samples that are traceable from the periphery to the CNS. Specific Aim 2 will evaluate the hypothesis that CIS-related activation of the complement system in the brain of DISC1 mutant mice will be exacerbated by early postnatal infection with Toxoplasma gondii, leading to abnormal development of GABA interneuron and dendritic spines in the frontal cortex.

精神分裂症患者对传染性抗原和食物抗原的体液免疫增强。增加