Neuronal basis of sensory processing dysfunction in schizophrenia

精神分裂症感觉处理功能障碍的神经元基础

• 批准号: 8105222
• 负责人: STEPHEN D GINSBERG
• 金额: $ 20.83万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105222
• 关键词: Affect; Auditory area; Autopsy; Biological Preservation; Brain; Brain region; Calcium-Binding Proteins; Cell Density; Cells; Chronic; Control Groups; Coupled; Custom; Disease; Down-Regulation; Experimental Models; Failure; Functional disorder; Funding; Gene Expression; Gene Expression Alteration; Gene Expression Profiling; Gene Family; Genes; Glutamates; Goals; Hippocampus (Brain); Impaired cognition; Impairment; Individual; Interneurons; Lead; Link; Measurement; Measures; Mental disorders; Methods; Modeling; Molecular Profiling; Monkeys; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neurocognitive; Neuronal Dysfunction; Neurons; Nuclear Protein; Nuclear Proteins; Outcome; Parvalbumins; Pathway interactions; Patients; Pattern; Phencyclidine; Population; Prefrontal Cortex; Process; Processed Genes; Pyramidal Cells; Relative (related person); Saline; Sampling; Schizophrenia; Sensory; Sensory Process; Site; Staining method; Stains; Techniques; Visual; Visual Cortex; area striata; base; calbindin; calretinin; cell type; density; design; gamma-Aminobutyric Acid; immunocytochemistry; information processing; laser capture microdissection; mRNA Expression; mind control; neural circuit; research study; sensory cortex; stellate cell

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive dysfunction is a core feature of the disorder, reflecting widespread cortical and subcortical neuronal dysfunction. The goal of the overall Center is to investigate mechanisms underlying sensory processing disturbances in schizophrenia, with particular emphasis on glutamatergic/NMDA-related mechanisms. Cortical processing disturbances in schizophrenia in general have been linked to altered expression of calcium binding proteins within GABA-ergic interneurons, possibly reflecting secondary down regulation due to primary failure in glutamatergic drive. This Project will examine cell density and gene expression profiles of GABA-ergic interneurons in primary visual cortex in schizophrenia, using laser capture microdissection coupled with gene array expression techniques developed at NKI/NYUSoM by the Project Leader, Dr. Ginsberg, and will build as well from a prior gene array study of hippocampal stellate cells in schizophrenia showing reduced NMDA receptor-related expression. The project co-leader. Dr. Smiley, is an expert histologist who is pursuing ongoing studies of calcium binding protein/GABA interneuron density in auditory cortex as part of an NlMH-funded project. Decreased parvalbumin expression has been extensively documented in prefrontal cortex in schizophrenia, but sensory regions have been studied to only a limited degree. For the NKI component of the study, quantitative morphometric analyses will be performed on postmortem visual cortex from schizophrenia and control subjects. Immunocytochemistry will be used to identify GABA interneuron cell types, including pavalbumin, calbindin and calretinin cell types. Relative density of GABA interneurons will then be compared between schizophrenia and control groups. Finally, using laser capture microdissection, select populations of calbindin and parvalbumin neurons will be obtained and processed for gene array analysis by Dr. Ginsberg. Gene array analysis will analyze expression level of calcium binding proteins, glutamate-related constructs and other more general gene families.

精神分裂症是一种主要的精神疾病，影响约 1% 的人口 全世界。认知功能障碍是该疾病的核心特征，反映了广泛的皮质 和皮质下神经元功能障碍。整个中心的目标是研究机制 精神分裂症潜在的感觉处理障碍，特别强调 谷氨酸能/NMDA 相关机制。精神分裂症的皮质处理障碍 一般与 GABA 能细胞内钙结合蛋白表达的改变有关 中间神经元，可能反映由于谷氨酸能的原发性衰竭导致的继发性下调 驾驶。该项目将检查 GABA 能的细胞密度和基因表达谱 精神分裂症初级视觉皮层的中间神经元，使用激光捕获显微切割耦合 项目负责人 Dr. NKI/NYUSoM 开发的基因阵列表达技术 金斯伯格，也将从之前对海马星状细胞的基因阵列研究中构建 精神分裂症显示 NMDA 受体相关表达减少。项目共同负责人。博士。 Smiley 是一位组织学家专家，正在进行钙结合蛋白/GABA 的研究 作为 NlMH 资助项目的一部分，听觉皮层的中间神经元密度。小清蛋白减少 精神分裂症患者的前额皮质中的表达已被广泛记录，但感觉 地区的研究只达到了有限的程度。对于该研究的 NKI 部分， 将对死后视觉皮层进行定量形态测量分析 精神分裂症和对照受试者。免疫细胞化学将用于鉴定 GABA 中间神经元细胞类型，包括新白蛋白、钙结合蛋白和钙视网膜蛋白细胞类型。相对密度 然后将比较精神分裂症组和对照组之间的 GABA 中间神经元。最后， 使用激光捕获显微切割，选择钙结合蛋白和小白蛋白神经元群 由金斯伯格博士获得并处理用于基因阵列分析。基因阵列分析会分析 钙结合蛋白、谷氨酸相关结构和其他更一般的表达水平 基因家族。