PROJECT 3: MOLECULAR & CELLULAR INTEGRITY OF THE SEROTONIN SYSTEM IN DEPRESSION

项目 3:分子

基本信息

  • 批准号:
    8167934
  • 负责人:
  • 金额:
    $ 21.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-07-01 至 2011-06-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A variety of postmortem brain studies and clinical investigations have provided evidence that serotonin neurotransmission is reduced in the brain of subjects diagnosed with major depression. While the clinical and postmortem studies have provided a valuable contribution towards understanding the role of serotonin in the pathophysiology of depression, it remains unclear what specific neurochemical substrate or mechanism is responsible for the deficit in serotonin neurotransmission in major depression. It is also important to note that worldwide women have twice the rate of depression as that of men, and several clinical studies have documented gender-specific differences in treatment responses and in structural and functional brain imaging measurements. Many lines of evidence suggest that ovarian hormones play a role in women's greater vulnerability to depression, and estrogen has been shown to modulate serotonin function. Although progress is being made in understanding the pathophysiology of depression, it remains unknown what the biological mechanisms are that make women vulnerable to developing depressive disorders. This proposal is intended to test the hypothesis that there is a gender-specific alteration in the biosynthesis of one or more key neuronal regulators of serotonin synthesis or neuronal activity which produces a deficit in serotonin neurotransmission in midbrain serotonin neurons of female subjects diagnosed with major depression. The specific aims of this grant proposal are intended to determine the biosynthetic integrity of very specific serotonin-related molecules such as the rate-limiting enzyme for serotonin synthesis, tryptophan hydroxylase, 5-HT1A autoreceptors, serotonin-related transcription factors and important afferent neuromodulators in specific brain regions of subjects diagnosed with major depression. The experiments will be conducted on human postmortem brain specimens of both female and male subjects diagnosed with major depression and matched non-psychiatric control subjects. To determine that the biochemical and cellular changes in depressed subjects are not resulting from the possible confounding influence of antidepressant treatment, the human postmortem biochemical measurements will be compared to identical biochemical measurements conducted in the same brain regions of non-human male and female primates that have been chronically treated with an antidepressant. The studies will utilize several histological, biochemical and molecular biological procedures to quantify protein and gene expression of the various serotonergic molecules in tissue specimens containing the midbrain dorsal raphe nucleus and prefrontal cortex. Understanding the biochemical mechanisms contributing to the alterations in serotonin biosynthesis and neurotransmission in depression, with a special emphasis on gender influences, will provide important information regarding the pathophysiology of the serotonin system in depressive illness that may lead to developing new treatment strategies for depression, particularly in women.
这个子项目是众多研究子项目之一

项目成果

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MARK C AUSTIN其他文献

MARK C AUSTIN的其他文献

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{{ truncateString('MARK C AUSTIN', 18)}}的其他基金

PROJECT 3: MOLECULAR & CELLULAR INTEGRITY OF THE SEROTONIN SYSTEM IN DEPRESSION
项目 3:分子
  • 批准号:
    8360508
  • 财政年份:
    2011
  • 资助金额:
    $ 21.7万
  • 项目类别:
MOLECULAR BIOLOGY CORE
分子生物学核心
  • 批准号:
    8360505
  • 财政年份:
    2011
  • 资助金额:
    $ 21.7万
  • 项目类别:
MOLECULAR BIOLOGY CORE
分子生物学核心
  • 批准号:
    8167931
  • 财政年份:
    2010
  • 资助金额:
    $ 21.7万
  • 项目类别:
MOLECULAR BIOLOGY CORE
分子生物学核心
  • 批准号:
    7959828
  • 财政年份:
    2009
  • 资助金额:
    $ 21.7万
  • 项目类别:
PROJECT 3: MOLECULAR & CELLULAR INTEGRITY OF THE SEROTONIN SYSTEM IN DEPRESSION
项目 3:分子
  • 批准号:
    7959831
  • 财政年份:
    2009
  • 资助金额:
    $ 21.7万
  • 项目类别:
MOLECULAR BIOLOGY CORE
分子生物学核心
  • 批准号:
    7720503
  • 财政年份:
    2008
  • 资助金额:
    $ 21.7万
  • 项目类别:
PROJECT 3: MOLECULAR & CELLULAR INTEGRITY OF THE SEROTONIN SYSTEM IN DEPRESSION
项目 3:分子
  • 批准号:
    7720506
  • 财政年份:
    2008
  • 资助金额:
    $ 21.7万
  • 项目类别:
COBRE: UMMC: RR CORE E: MOLECULAR BIOLOGY CORE FACILITY
COBRE:UMMC:RR 核心 E:分子生物学核心设施
  • 批准号:
    7610490
  • 财政年份:
    2007
  • 资助金额:
    $ 21.7万
  • 项目类别:
INTEGRITY OF THE DORSAL RAPHE SEROTONIN SYSTEM IN ALCOHOL DEPENDENCE AND SUICIDE
中缝背侧血清素系统的完整性在酒精依赖和自杀中的作用
  • 批准号:
    7610493
  • 财政年份:
    2007
  • 资助金额:
    $ 21.7万
  • 项目类别:
COBRE: UMMC: ADMINISTRATIVE CORE
COBRE:UMMC:管理核心
  • 批准号:
    7610486
  • 财政年份:
    2007
  • 资助金额:
    $ 21.7万
  • 项目类别:
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