Sex, Sex Steroids & Neuroprotection

性、性类固醇

• 批准号: 7383757
• 负责人: PATRICIA D. HURN
• 金额: $ 132.09万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383757
• 关键词: Sex; Steroids; Neuroprotection

DESCRIPTION (provided by applicant): It is now well recognized that estrogens and androgens strongly modulate injury in CNS regions completely unrelated to reproductive function or sexual differentiation. These steroids protect (and in restricted conditions, can exacerbate) the neuronal response to injury from ischemic, inflammatory and immunological challenges. The major aim of this program is to 1) dissect important mechanisms by which the principal mammalian estrogen, 17$ estradiol, rescues neurons from experimental stroke, cerebral ischemia and multiple sclerosis and 2) open new territory by understanding the male phenotype of ischemic sensitivity and the role of testosterone in this phenotype. The Program has several important strengths. First, strong investigators with critical expertise have been integrated in the Program. Our preliminary data indicate feasibility of our approaches and demonstrate the potential for significant new knowledge to emerge in the new area of gender-based pathobiology. The investigators are leaders in their fields concerning mechanisms of neuronal function in health and disease. We now sharply focus that expertise on sex and sex steroids, a topic traditionally found of interest only to endocrinology and reproductive medicine. Second, the investigators use sophisticated experimental approaches to evaluate mechanism-oriented hypotheses. Finally, this program is highly novel, one of few to seek out how sex steroids interact with generalized cell death/survival pathways. Instead of minimizing or excluding sex and sex steroids as is commonly done in translational research, the present experimental approach maximizes them. Our findings will elucidate the mechanisms behind a most fundamental "genetic" aspect of disease: biological sex. The Program consists of 3 projects :!) Role of Cocaine Amphetamine Regulated Transcript (CART) in Estrogen mediated Neuroprotection, 2) Testosterone and Cerebral Ischemia, 3) Neuroprotective effects of estrogen and testosterone in experimental autoimmune encephalomyelitis (EAE). These projects are supported by 3 core facilities: 1) Administration; 2) Tissue Analysis and 3) Animal Models.

描述（由申请人提供）： 现在公认雌激素和雄激素强烈调节CNS区域的损伤，与生殖功能或性分化完全无关。这些类固醇保护（并且在限制条件下，可以加剧）神经元对缺血性损伤、炎症和免疫挑战的反应。该计划的主要目的是：1）解剖重要的机制，其中主要的哺乳动物雌激素，17 β雌二醇，从实验性中风，脑缺血和多发性硬化症和2）通过了解缺血敏感性的男性表型和睾酮在这种表型中的作用，打开新的领域拯救神经元。该方案有几个重要的优势。首先，具有关键专业知识的强有力的调查人员已被纳入该方案。我们的初步数据表明，我们的方法的可行性，并展示了显着的新知识，以性别为基础的病理生物学的新领域出现的潜力。这些研究者是各自领域的领导者，涉及健康和疾病中神经元功能的机制。我们现在将专业知识集中在性和性类固醇上，这是一个传统上只对内分泌学和生殖医学感兴趣的话题。其次，研究人员使用复杂的实验方法来评估机制导向的假设。最后，这个项目非常新颖，是少数几个寻找性类固醇如何与广义细胞死亡/存活途径相互作用的项目之一。而不是最小化或排除性和性类固醇是通常在转化研究中做的，本实验方法最大化他们。我们的发现将阐明疾病最基本的“遗传”方面背后的机制：生物性别。该计划包括三个项目：）CART在雌激素介导的神经保护中的作用，2）睾酮和脑缺血，3）雌激素和睾酮在实验性自身免疫性脑脊髓炎（EAE）中的神经保护作用。这些项目由3个核心设施支持：1）管理; 2）组织分析和3）动物模型。