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: 8324640
• 负责人: STEPHEN D GINSBERG
• 金额: $ 21.11万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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/8324640
• 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; Outcome; Parvalbumins; Pathway interactions; Patients; Pattern; Phencyclidine; Population; Prefrontal Cortex; Process; Processed Genes; Pyramidal Cells; Relative (related person); Research; 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障碍，影响约1%的人口 国际吧认知功能障碍是该疾病的核心特征，反映了广泛的皮质 和皮层下神经元功能障碍整个中心的目标是调查机制 精神分裂症的潜在感觉处理障碍，特别强调 多巴胺能/NMDA相关机制。精神分裂症患者的大脑皮层加工障碍 一般与GABA能神经元内钙结合蛋白的表达改变有关。 中间神经元，可能反映了继发性下调，由于原发性失败，在脑电 驱动本项目将研究GABA能神经细胞的细胞密度和基因表达谱， 应用激光捕获显微切割技术研究精神分裂症初级视皮层中间神经元 与基因阵列表达技术开发的NKI/NYUSoM的项目负责人，博士。 Ginsberg，并将建立，以及从先前的基因阵列研究海马星状细胞， 精神分裂症表现出减少的NMDA受体相关的表达。项目的共同领导者。博士 Smiley是一位组织学专家，正在进行钙结合蛋白/GABA的研究。 听觉皮层中的中间神经元密度，作为NIMH资助项目的一部分。小清蛋白减少 在精神分裂症患者的前额叶皮层中有广泛的表达记录，但在感觉上， 对这些区域的研究程度有限。对于研究的NKI部分， 将对死后视觉皮层进行定量形态测定分析， 精神分裂症和对照组。将使用免疫细胞化学来鉴定GABA 中间神经元细胞类型，包括pavalbumin、calbindin和calretinin细胞类型。相对密度 然后将精神分裂症组和对照组之间的GABA中间神经元进行比较。最后， 使用激光捕获显微切割，选择钙结合蛋白和小清蛋白神经元的群体， 由金斯伯格博士进行基因阵列分析。基因阵列分析将分析 钙结合蛋白、谷氨酸相关构建体和其他更一般的表达水平 基因家族