Neuroanatomy and molecular neurobiology of suicide

自杀的神经解剖学和分子神经生物学

• 批准号: 6480783
• 负责人: Victoria Arango
• 金额: $ 17.72万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480783
• 关键词: alcoholism /alcohol abuse; autoradiography; behavioral /social science research tag; behavioral genetics; brain mapping; clinical depression; clinical research; gene expression; genetic mapping; human subject; human tissue; immunocytochemistry; microarray technology; neurochemistry; postmortem; serotonin receptor; serotonin transporter; suicide; transcription factor; tryptophan 5 monooxygenase

This project aims to utilize the unique resources of the Human Neurobiology Core Brain Bank to investigate further our hypothesis of behavior disinhibition, mediated by deficits in the ventrolateral prefrontal cortex, that lead to suicidal behavior. Project 2A (Ventral Prefrontal Cortex) has four components: (1) systematic cytoarchitectonic investigation of ventrolateral and dorsal prefrontal cortex of suicides and controls, to determine neuron density. This serves as an index to be able to obtain correlations with the numbers of brainstem serotonergic and noradrenergic source neurons, as well as with receptor density measures in the brainstem and cortex; (2) Association studies of candidate genes with suicide and central serotonin function (Assays will be done by the Clinical Laboratory Core); (3) Development and application of microarray technology to analyze gene expression in brain areas of interest of depressed and non-depressed suicides, depressed and non- depressed non-suicides (Assays will be done by the Clinical Laboratory Core); and (4) 5-HT/2C receptor pre-mRNA editing in suicide victims (depressed and non-depressed) and normal controls, followed by 5- HT/2A/2C receptor agonist-promoted binding of 35S-GTPgammaS in membrane homogenates. Project 2B proposes a series of gene expression studies in the serotonergic DRN of suicide victims and depressed and non-depressed controls, including the serotonin transporter, 5-HT1A receptor, tryptophan hydroxylase and select transcription factors (e.g. pCREB). Alcoholics represent a high-risk population for suicide and Project 2C proposes to study the serotonergic neurons of alcoholic suicides, alcoholic non-suicides and controls by immunocytochemistry and immunoautoradiography. The proposed cytoarchitectonic and molecular biological approaches aim to identify possible sites of abnormality in the brainstem and cortex of four groups; suicide victims, non-psychiatric non-suicide controls, and two other non-suicide control groups: depressed and alcoholics.

该项目旨在利用人类神经生物学核心脑库的独特资源来进一步研究我们对行为抑制作用的假设，这是由腹外侧前额叶皮层缺陷介导的，导致了自杀行为。项目2a（腹前额叶皮层）具有四个组成部分：（1）自杀和对照组的腹外侧和背侧前额叶皮层的系统细胞结构研究，以确定神经元密度。这是能够获得与脑干血清素能和去甲肾上腺素能神经元的数量以及脑干和皮层中受体密度测量值的相关性的指数； （2）候选基因与自杀和中央5-羟色胺功能的关联研究（测定将由临床实验室核心进行）； （3）开发和应用微阵列技术来分析抑郁症和非抑郁自杀，抑郁和非抑郁的非自杀的大脑区域中基因表达（分析将由临床实验室核心进行）； （4）在自杀受害者（抑郁和不抑郁）和正常对照中的5-HT/2C受体Pre-MRNA编辑，其次是5-HT/2A/2C受体受体激动剂激动剂激动剂促进的结合，对膜含量的35S-GTPGAMMAS的结合。 Project 2b提出了在自杀受害者的血清素能DRN和抑郁和非抑郁的控制中提出的一系列基因表达研究，包括5-羟色胺转运蛋白转运蛋白，5-HT1A受体，色氨酸羟化酶和精选的转录因子（例如PCREB）。酗酒者代表自杀的高风险人群，项目2C提议研究酗酒自杀，酗酒非杀菌剂和通过免疫细胞化学和免疫功能学的对照的血清素能神经元。提出的细胞结构和分子生物学方法旨在确定四组脑干和皮质中可能的异常部位。自杀受害者，非精神病患者的非精神病患者和其他两个非自杀对照组：抑郁症和酗酒者。