Imaging neurotoxicity: The effect of anti-NMDAR Ab on hippocampus and amygdala in

影像神经毒性：抗 NMDAR 抗体对海马和杏仁核的影响

• 批准号: 8122315
• 负责人: Joy Hirsch
• 金额: $ 25.72万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 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/8122315
• 关键词: Age; Amygdaloid structure; Anti-DNA Antibodies; Antibodies; Autoantibodies; Autoimmune Diseases; Behavioral; Binding; Blood - brain barrier anatomy; Cardiolipins; Cessation of life; Clinical Trials; Cognition; Cognitive; Cohort Analysis; Cohort Studies; Cross-Sectional Studies; DNA; Disease; Emotional; Emotions; Functional Magnetic Resonance Imaging; Functional disorder; Gender; Glutamates; Goals; Hippocampus (Brain); Hypertensive Episode; Image; Impaired cognition; Impairment; Individual; Infection; Institutes; Lupus; Magnetic Resonance; Measurement; Measures; Mediating; Medical Research; Memory; Mental Depression; Methodology; Modality; Mood Disorders; Moods; Mus; N-Methyl-D-Aspartate Receptors; Neuraxis; Neurologic; Neuronal Dysfunction; Neurons; Nuclear; Onset of illness; Outcome Measure; Pathogenesis; Patients; Pharmaceutical Preparations; Play; Process; Research Personnel; Role; Serum; Signal Transduction; Stress; Systemic Lupus Erythematosus; Techniques; Testing; Time; Universities; cognitive change; cognitive function; cohort; conditioned fear; design; experience; functional disability; illness length; neuron apoptosis; neuroprotection; neuropsychological; neurotoxicity; preconditioning; prevent; relating to nervous system; response; secondary outcome; time interval; time use; tool

Project 3: "Imaging neurotoxicity: The effect of anti-NMDAR Ab on hippocampus and amygdala in NPSLE patients" (Hirsch, PI) Systemic lupus erythematosus is an autoimmune disease characterized by the presence of anti-nuclear antibodies, especially antibodies to DNA. Patients with lupus develop, over time, cognitive impairment and mood disorders. We have identified a subset of anti-DNA antibodies that cross-reacts with the NR2A and NR2B subunits of the NMDA receptor (NMDAR). In mice, antibodies with this crossreactivity can cause apoptosis of neurons in the hippocampus or the amygdala, leading to cognitive impairment or behavioral dysfunction, respectively. We hypothesize that antibody, together with a breach in the blood-brain barrier, can damage the hippocampus and amygdala in lupus patients, and that insults that open the blood-brain barrier accumulate over time. This project is designed to assess whether functional Magnetic Resonance Imagining (fMRI) is a sensitive modality to assess cognitive function and emotional response in patients with SLE and whether the subset of anti-DNA antibodies that cross-reacts with the NMDAR associates with impairment. We will determine whether patients with anti-NMDAR antibodies acquire impairment over time using fMRI to assess activity in the hippocampus and the amygdala, regions subserving cognition and emotional memory. Two studies are proposed: a cohort analysis to determine whether antibody associates with impairment in patients with disease for 10 or more years, and whether antibody associates with early impairment in patients with disease for less than 2 years. The second study is a longitudinal assessment of patients to determine if fMRI can detect change over a 6 month time interval. This study is a necessary precondition to a clinical trial of neuroprotection in SLE.

项目3：“成像神经毒性：抗NMDAR抗体对海马和杏仁核的影响， NPSLE患者”（Hirsch，PI） 系统性红斑狼疮是一种自身免疫性疾病，其特征是存在抗核抗体。 抗体，尤其是DNA抗体。随着时间的推移，狼疮患者会出现认知障碍 和情绪障碍我们已经确定了一个子集的抗DNA抗体，交叉反应的 NMDA受体（NMDAR）的NR2A和NR2B亚基。在小鼠中，具有这种交叉反应性的抗体 会导致海马体或杏仁核中的神经元凋亡， 损伤或行为功能障碍。我们假设，抗体，连同一个 血脑屏障的破坏，会损害狼疮患者的海马体和杏仁核， 开放血脑屏障的损伤会随着时间的推移而累积。 该项目旨在评估功能性磁共振成像（fMRI）是否是一种 敏感的方式来评估SLE患者的认知功能和情绪反应， 与NMDAR交叉反应的抗DNA抗体亚群与损伤有关。我们 将使用fMRI确定抗NMDAR抗体的患者是否会随着时间的推移而受损 评估海马体和杏仁核的活动，这些区域负责认知和情感 记忆提出了两项研究：队列分析，以确定抗体是否与 疾病患者的损害10年或更长时间，以及抗体是否与早期 患病时间少于2年的患者。第二项研究是纵向评估 以确定fMRI是否可以检测到6个月时间间隔内的变化。本研究是一项 这是SLE神经保护临床试验的必要前提。