Cortico-thalamic Glutamate/GABA mRNA in schizophrenia

精神分裂症中的皮质丘脑谷氨酸/GABA mRNA

基本信息

批准号：
7233626
负责人：
VAHRAM HAROUTUNIAN
金额：
$ 27.63万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7233626
关键词：
Affect Alzheimer&apos s Disease Anterior Area Atrophic Autopsy Biochemical Biological Markers Brain Cell Count Cell Nucleus Cerebral cortex Chronically Ill Clinical Deformity Dependence Diagnosis Elderly Enzymes Etiology Excitotoxic lesion Failure Functional disorder Glutamate Decarboxylase Glutamate Receptor Glutamates Image Investigation Laboratories Lateral Lateral Geniculate Body Lead Lesion Measurement Measures Medial Dorsal Nucleus Messenger RNA Molecular Neocortex Nerve Degeneration Neurons Nuclear Pattern Population Prefrontal Cortex Probability Process Proteins Pulvinar structure Purpose Rattus Receptor Gene Schizophrenia Severities Specimen Structure of inferior temporal gyrus Structure of postcentral gyrus System Temporal Lobe Testing Thalamic Nuclei Thalamic structure Ventral Lateral Thalamic Nucleus Visual Cortex area striata brain tissue cingulate cortex comparative density design experience frontal lobe gamma-Aminobutyric Acid mRNA Expression mRNA Stability neocortical neurochemistry neuron loss older patient protein expression receptor research study response size

项目摘要

DESCRIPTION (provided by applicant): Glutamatergic/GABAergic system abnormalities in the cerebral cortex and morphological/anatomical/biochemical abnormalities in the thalamus are present in schizophrenia. Some of the evidence comes from studies conducted in our laboratories showing changes in the expression of mRNAs encoding for ionotropic glutamate receptor genes in both the thalamus and the cortex, and for the GABA synthesizing enzyme glutamic acid decarboxylase (GAD-65 and GAD-67). Studies on the same brain specimens derived from extremely well characterized neuropsychiatrically and neuropathologically assessed schizophrenic subjects has shown that GAD mRNA level changes are reflected in functional abnormalities in the activity of GAD. The studies proposed aim to determine whether glutamatergic/GABAergic abnormalities in the neocortex are associated with glutamatergic/GABAergic abnormalities in the thalamus. Brain tissue specimens will be derived from: Dorsolateral prefrontal cortex (DLPFC) and the mediodorsal nucleus (MDN) of the thalamus; Cingulate cortex and the anterior group of thalamic nuclei; Precentral cortex (Brodmann 4/6) and the ventrolateral nuclear group of the thalamus; Inferior temporal gyrus (Brodmann 20) and the pulvinar; and Striate / Visual cortex (Brodmann 17) and the lateral geniculate nucleus of the thalamus. These specimens will be derived from 37 normal controls, 32 antemortem assessed and diagnosed schizophrenics who have been neuropathologically characterized to be free of any confounding neuropathological lesions, and 15 Alzheimer disease cases for comparative purposes. We will test hypotheses designed to determine whether glutamatergic and GABAergic abnormalities (mRNA and protein) in specific thalamic nuclei are associated with glutamatergic and GABAergic abnormalities in specific cortical regions and vice versa. In addition, studies in rats will test the hypothesis that the glutamatergic and GABAergic abnormalities in the prefrontal cortex are a direct result of lesions in the MDN.

描述（由申请人提供）：丘脑丘脑中存在脑皮质和形态/解剖学/生化异常的谷氨酸/GABA能系统异常。一些证据来自在我们的实验室中进行的研究，表明丘脑和皮质中的离子型谷氨酸受体基因的mRNA表达变化，以及GABA合成酶谷氨酸十羧酸酶（GAD-65和GAD-65和GAD-67）的GABA合成酶。对来自极为表征的神经精神和神经病理学评估的精神分裂症受试者的相同大脑标本的研究表明，GAD mRNA水平的变化反映在GAD活性中的功能异常中。研究旨在确定新皮层中的谷氨酸能/GABA能异常是否与丘脑中的谷氨酸能/GABA能异常有关。脑组织标本将源自：丘脑的背外侧前额叶皮层（DLPFC）和中型核（MDN）；扣带皮层和丘脑核的前组；丘脑前后皮层（Brodmann 4/6）和丘脑的腹外侧核群；下颞回（Brodmann 20）和Pulvinar；丘脑的侧面 /视觉皮层（Brodmann 17）和侧向核核。这些标本将源自37个正常对照，32个被评估和诊断为神经病理学的精神分裂症患者，这些精神分裂症患者在神经病理学上表征不含任何混杂的神经病理病变，以及15例阿尔茨海默氏病病例，以进行比较。我们将检验旨在确定特定丘脑核中谷氨酸能和GABA能异常（mRNA和蛋白）是否与特定皮质区域的谷氨酸能和GABA能异常相关的假设，而visea是与谷氨酸能和GABA能异常有关的。此外，对大鼠的研究将检验以下假设：前额叶皮层中谷氨酸能和GABA能异常是MDN病变的直接结果。