Limbic Lobe in Schizophrenia and Bipolar Disorder

精神分裂症和躁郁症的边缘叶

基本信息

批准号：
7195559
负责人：
FRANCINE M. BENES
金额：
$ 50.85万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7195559
关键词：
Accounting Actins Acute Address Affect Age Algorithms Alzheimer&apos s Disease Am 80 Anterior Anticonvulsants Antipsychotic Agents Antisense RNA Apical Apoptosis Apoptotic Appendix Archives Area Astrocytes Autopsy Award Axon BAK1 gene BAX gene Base Pairing Bax protein Biological Assay Bipolar Disorder Brain Brain imaging Bulla Caspase Cell Count Cell Death Cell Density Cell Nucleus Cell Survival Celloidin Cells Cereals Characteristics Chlorpromazine Chromatin Chromosome Pairing Chronic Collecting Cell Compatible Complementary DNA Complex Condition Count Cytolysis DNA DNA Damage DNA Fragmentation DNA Repair DNA Repair Enzymes DNA Single Strand Break Data Data Collection Data Set Dendrites Development Devices Diagnosis Diffuse Digoxigenin Disease Dopamine Dopamine D1 Receptor Dose Drug Metabolic Detoxication ESD Gene Employee Strikes Emulsions Environmental Risk Factor Enzymes Exposure to Fiber Figs - dietary First Degree Relative Follow-Up Studies Frequencies Frozen Sections Functional disorder Funding Future Gender Gene Expression Gene Expression Profiling Genes Genomics Glutamate Decarboxylase Glutamate Receptor Glutamates Glutathione S-Transferase Grant Granzyme Graph Growth HPRT1 gene Hand Handedness Heritability Hippocampal Formation Hippocampus (Brain)Housekeeping Gene Human Hydrolase Hypoxanthine Phosphoribosyltransferase In Situ In Situ Hybridization Individual Interneurons JNK-activating protein kinase JUN gene Kainic Acid Receptors L-Type Calcium Channels Label Laboratories Laboratory Study Left Ligands Light Lithium Lithium Carbonate Localized MAP3K1 gene MAPK8 gene Manuscripts Masks Measures Mediating Messenger RNA Meta-Analysis Metabolic Metabolic Pathway Methodology Methods Microdissection Microscopic Molecular Mood Disorders Moods N-Methyl-D-Aspartate Receptors N-Methylaspartate NF-kappa B NOS1 gene NOS1 protein, human Nature Necrosis Neurofibrillary Tangles Neuroglia Neuronal Dysfunction Neurons Nitric Oxide Synthase Type I Nonparametric Statistics Nuclear Numbers Oligonucleotides Optics Oxidative Stress Parkinson Disease Pathway interactions Patients Pattern Pharmaceutical Preparations Play Poly(ADP-ribose) Polymerases Polymerase Polymerase Chain Reaction Population Predisposition Prefrontal Cortex Preparation Protein Isoforms Psychiatry Psychotic Disorders Publications Publishing Quality Control RNA RNA amplification Range Rattus Reactive Oxygen Species Regulation Reporting Research Resolution Reverse Transcriptase Polymerase Chain Reaction Rodent Model Role Sampling Schizophrenia Severities Shapes Signal Transduction Silver Site Solutions Spectrophotometry Staining and Labeling Staining method Stains Sterility Stress Study Section Subgroup Substantia nigra structure Superoxide Dismutase Susceptibility Gene Synapses System TNF receptor-associated factor 1 TNFSF10 gene TP53 gene Techniques Testing Therapeutic Thinking Time Tissues Transcript Tube Tumor Necrosis Factor Ligand Superfamily Member 6 Tyrosine 3-Monooxygenase Up-Regulation Work alveus apoptotic protease-activating factor 1 base brain tissue c-myc Genes caspase-2 caspase-8 catalase cell injury cingulate cortex cohort comparison group cryostat density dentate gyrus design disturbance in affect dopamine system dopaminergic neuron dosage endophenotype experience gamma-Aminobutyric Acid genetic regulatory protein glutathione peroxidase glutathione synthase hippeastidine hippocampal pyramidal neuron human study laser capture microdissection limbic lobe mRNA Expression neural circuit neuronal cell body neuropsychiatry novel perforin receptor repair enzyme response selective expression sex size trend two-dimensional

项目摘要

DESCRIPTION (provided by applicant): This is a resubmission of a competitive renewal application (ROl MH42261-14) for postmortem studies of the limbic lobe in relation to schizophrenia (SZ) and bipolar disorder (BD). Recent work from this laboratory has demonstrated a series of microscopic anomalies in layer II of the anterior cingulate cortex (ACCx-ll) and sectors CA3 and CA2 of the hippocampal formation (HIPP) in SZs and BDs. These changes have included reductions in interneurons, although an overt loss of GABA cells now appears to be a striking feature of GD, but not SZ. Even so, both SZs and BDs show evidence for a decrease of GABAergic function in ACCx-ll and HIPP. Specific Aim I will test the hypothesis that discrepancies in cell counting data in ACCx and HIPP of SZs and/or BDs can be explained in part by differences in sampling window size employed in 2D vs 3D counting. Specific Aim II will test the hypothesis that there will be a reduction in cells positive for GAD in HIPP sectors CA3 and CA2, as well as layers II and Ill of ACCx in BDs, but not SZs or their family members. In addition, it is also postulated that dopaminergic inputs to GABA cells are in increased in ACCx-ll of SZs, but not BDs. Specific Aim Ill will test the hypothesis that in ACCx and HIPP of SZs and their first degree relatives there will be a decrease of the kainate receptor in PNs, while the NMDA receptor will be decreased in NPs. Specific Aim IV will test the hypothesis that neurons in SZs will show less evidence of apoptosis than patients with BD and this will be especially apparent in interneurons. Taken together, the proposed studies are seeking to identify specific aspects of limbic circuitry that may be involved in the induction of neuronal pathology in SZ and BD. By learning more about the possible role of oxidative stress, novel forms of pharmacotherapy for the major neuropsychiatric disorders may eventually be developed.

描述（由申请人提供）：这是竞争更新的重新提交应用（ROL MH42261-14）用于边缘叶的验尸研究精神分裂症（SZ）和躁郁症（BD）。该实验室的最新工作在前扣带回的II层中证明了一系列微观异常 SZS中海马形成（HIPP）的皮层（ACCX-LL）和CA3和CA2 BDS。这些变化包括降低中间神经元的降低，尽管明显的损失 GABA细胞现在似乎是GD的引人注目的特征，但不是SZ。即便如此，SZS和 BDS显示出ACCX-LL和HIPP中GABA能功能降低的证据。具体目的i 将检验以下假设：ACCX和SZS中的细胞计数数据差异和/或BD可以部分通过2D中使用的采样窗口大小的差异来解释 vs 3D计数。具体目标II将检验以下假设 HIPP扇区Ca3和Ca2中GAD阳性的细胞，以及II层和ACCX IL 在BDS中，但不是SZS或其家人。此外，还假设在SZS的ACCX-LL中，对GABA细胞的多巴胺能输入量增加，但不增加BDS。特定目标将检验以下假设，即SZS和HIPP中的第一个假设学位亲属将降低PNS中的海藻酸盐受体，而NMDA会减少 NP中的受体将降低。特定目标IV将检验神经元的假设在SZ中，与BD患者相比，SZS的凋亡证据更少，这将是在中间神经元中尤其明显。综上所述，拟议的研究正在寻求确定可能参与诱导的边缘电路的特定方面 SZ和BD中的神经元病理学。通过更多地了解氧化的可能作用压力，主要神经精神疾病的新型药物疗法可能最终被开发。