Project 1 - Microglial activation in DNRAb-mediated brain pathology in mice

项目 1 - DNRAb 介导的小鼠脑病理学中的小胶质细胞激活

基本信息

批准号：
10454330
负责人：
BRUCE Thomas VOLPE
金额：
$ 89.88万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10454330
关键词：
Acute Adult Albumins Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Animals Antibodies Antigen-Antibody Complex Apoptotic Autoantibodies Autoimmune Blood - brain barrier anatomy Blood Circulation Brain Brain Injuries Brain Pathology Cell Nucleus Cells Cerebrospinal Fluid Chronic Clinical Clinical Trials Complement 1q DNA Dendrites Development Disease Enzyme Inhibition Exhibits Exposure to Fc Receptor Functional disorder Genetic Transcription HMGB1 gene Hippocampus (Brain)Immune Immunize Impaired cognition Impairment In Vitro Ingestion Injury Interferon Type I Lead Ligand Binding Lipopolysaccharides Lupus Mediating Meta-Analysis Methodology Microglia Modeling Molecular Mus N-Methyl-D-Aspartate Receptors Nervous System Physiology Neuraxis Neuronal Dysfunction Neurons Neuropsychiatric Systemic Lupus Erythematosus Oligoclonal IgG Pathology Pathway interactions Patients Peptidyl-Dipeptidase A Pharmaceutical Preparations Positron-Emission Tomography Property Receptor Activation Serum Site Slice Small Nuclear RNA Stress Study models Synapses Systemic Lupus Erythematosus TLR4 gene Testing Therapeutic Time brain dysfunction brain tissue central nervous system injury cognitive function cytokine druggable target ds-DNA excitotoxicity fetal human disease in vivo insight longitudinal analysis mouse model nerve injury neuroimaging neuron loss neuropsychiatric symptom pediatric patients prevent programs reconstitution release factor risk variant spatial memory targeted agent therapeutic target transcriptome sequencing

Acute Adult Albumins Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Animals Antibodies Antigen-Antibody Complex Apoptotic Autoantibodies Autoimmune Blood - brain barrier anatomy Blood Circulation Brain Brain Injuries Brain Pathology Cell Nucleus Cells Cerebrospinal Fluid Chronic Clinical Clinical Trials Complement 1q DNA Dendrites Development Disease Enzyme Inhibition Exhibits Exposure to Fc Receptor Functional disorder Genetic Transcription HMGB1 gene Hippocampus (Brain)Immune Immunize Impaired cognition Impairment In Vitro Ingestion Injury Interferon Type I Lead Ligand Binding Lipopolysaccharides Lupus Mediating Meta-Analysis Methodology Microglia Modeling Molecular Mus N-Methyl-D-Aspartate Receptors Nervous System Physiology Neuraxis Neuronal Dysfunction Neurons Neuropsychiatric Systemic Lupus Erythematosus Oligoclonal IgG Pathology Pathway interactions Patients Peptidyl-Dipeptidase A Pharmaceutical Preparations Positron-Emission Tomography Property Receptor Activation Serum Site Slice Small Nuclear RNA Stress Study models Synapses Systemic Lupus Erythematosus TLR4 gene Testing Therapeutic Time brain dysfunction brain tissue central nervous system injury cognitive function cytokine druggable target ds-DNA excitotoxicity fetal human disease in vivo insight longitudinal analysis mouse model nerve injury neuroimaging neuron loss neuropsychiatric symptom pediatric patients prevent programs reconstitution release factor risk variant spatial memory targeted agent therapeutic target transcriptome sequencing

展开

项目摘要

Project 1: Abstract We have shown that DNRAb, antibodies that cross-react with DNA and N-methyl D-aspartate receptor, cause cognitive impairment when they penetrate the hippocampus. The neural injury proceeds in two stages. First, there is excitotoxic neuronal death; second, there is microglial activation and dendritic loss in surviving neurons. Microglial suppression by angiotensin converting enzyme (ACE) inhibition restores neuronal integrity and cognitive function. We propose now to study the mechanism of microglial activation and dendritic loss and the mechanism of action of ACE inhibition. These studies have the potential to suggest additional therapeutic targets for ameliorating cognitive impairment in neuropsychiatric lupus.

项目1：抽象的我们已经证明了DNRAB，与DNA和N-甲基D-天冬氨酸交叉反应的抗体受体，当他们穿透海马时会引起认知障碍。神经损伤分两个阶段进行。首先，存在兴奋性神经元死亡。其次，有小胶质幸存神经元的激活和树突状丧失。血管紧张素抑制小胶质细胞转化酶（ACE）抑制恢复神经元完整性和认知功能。我们现在建议研究小胶质激活和树突状丧失的机制以及 ACE抑制的作用机理。这些研究有可能提出更多改善神经精神狼疮的认知障碍的治疗靶标。