NEUROPEPTIDE CO-EXPRESSION IN THE HYPOTHALAMUS

下丘脑中的神经肽共表达

• 批准号: 3402079
• 负责人: Paul E. Sawchenko
• 金额: $ 14.33万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402079
• 关键词: adrenalectomy; albino rat; catecholamines; corticotropin releasing factor; enkephalins; estrogens; gene expression; histochemistry /cytochemistry; homeostasis; hormone regulation /control mechanism; hypophysectomy; hypothalamus; immunochemistry; immunofluorescence technique; messenger RNA; neural information processing; neuroanatomy; neuroendocrine system; neuropeptides; oxytocin; peptide hormone biosynthesis; pituitary adrenal axis; steroid hormone; thyroid hormones; vasopressins

The proposed neuroanatomical studies employ immunohistochemical and hybridization histochemical methods to clarify the roles of particular hormonal and neural influences in regulating the expression of multiple neuroactive peptides that cohabit neurosecretory neuron populations in the rat hypothalamus. Parvocellular neurons that produce corticotropin-releasing factor for the initiation of pituitary-adrenal responses to stress, and magnocellular neurosecretory neurons that synthesize the peptide hormones oxytocin or vasopressin (which play roles reproduction and body water balance, respectively), are both known to express a number of additional neuropeptides. Differential effects of alterations in steroid hormones status have been described for both class of neurons. The proposed studies will address the following issues: 1. Non-steroidal influences on the CRF neuron. Evidence for roles of circulating corticotropin, thyroid hormones, and as yet unspecified stimuli associated with lactation will be characterized as to their effects on levels of co-existing peptides, their sites of action and/or whether effects on gene expression are involved. 2. Role of neural inputs in influencing peptide expression in the CRF neuron. The roles of projections arising from brainstem catecholamine neurons, the hippocampal formation, and the basal forebrain in mediating peptide dynamics in the CRF neuron, and\or in mediating the feedback effects of steroids will be assessed. The role of aminergic pathways in mediating responses to a specific stress model (hemorrhage) will also be evaluated. 3. Gonadal steroid effects on the magnocellular system. We have described pronounced and selective effects of manipulation of gonadal hormone status on the expression of coexisting peptides in magnocellular neurosecretory neurons of female rats. Systemic steroid replacement studies will be carried out in gonadectomized male rats to evaluate the generality and steroid specificity of the effect. Combined retrograde-transport -immunohistochemical methods will be used to determine whether the effect is specific to magnocellular neurons.

拟议的神经解剖学研究采用免疫组织化学和 用杂交组织化学方法阐明其作用 特殊的荷尔蒙和神经影响调节 共存的多种神经活性多肽的表达 大鼠下丘脑的神经分泌神经元亚群。 产生促肾上腺皮质激素释放因子的小细胞神经元 启动脑下垂体-肾上腺对压力的反应，以及 合成肽的大细胞神经分泌神经元 荷尔蒙催产素或加压素(起生殖作用) 和身体水分平衡)，都是已知的表达 一些额外的神经肽。差异化效应 已经描述了这两种情况下类固醇激素状态的变化 一类神经元。拟议的研究将涉及以下内容 问题： 1.非甾体激素对CRF神经元的影响。角色的证据 循环中的促肾上腺皮质激素，甲状腺激素，到目前为止 与哺乳有关的未指明的刺激将被描述 至于它们对共存多肽水平的影响，它们的位置 和/或是否涉及对基因表达的影响。 2.神经输入在影响大脑皮层多肽表达中的作用 CRF神经元。脑干投射的作用 儿茶酚胺神经元、海马结构和基底核 前脑在CRF神经元中介导肽的动力学，以及 在调节过程中，将评估类固醇的反馈效应。 胺能通路在介导对特定受体的反应中的作用 应激模型(出血)也将被评估。 3.性腺激素对大细胞系统的影响。我们有 描述了操纵的显著和选择性影响 性腺激素状态对共存多肽表达的影响 雌性大鼠的大细胞神经分泌神经元。系统性 类固醇替代研究将在性腺切除患者中进行 雄性大鼠评价类固醇激素的通用性和特异性 效果。联合逆行-转运-免疫组织化学 方法将用于确定效果是否为特定效果 到巨细胞神经元。