NEUROHORMONAL CONTROL OF SALT APPETITE & BLOOD PRESSURE

盐食欲的神经激素控制

• 批准号: 3385836
• 负责人: BRANDON G YONGUE
• 金额: $ 8.36万
• 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: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3385836
• 关键词: aldosterone; angiotensin /renin /aldosterone hypertension; angiotensinogen; appetite regulatory center; blood pressure; brain metabolism; cryostat; developmental genetics; familial hypertension; gene expression; genetic strain; hormone regulation /control mechanism; inbreeding; laboratory rat; linkage mapping; motivation; neuroendocrine system; neurohormones; psychological models; salt intake

The proposed experiments will investigate the relationship of brain aldosterone binding angiotensinogen gene expression to control of a model motivated behavior (salt consumption) and a regulated physiological process (the circulation). Genetic influences on these processes will be studied through analysis of phenotype variation in behavior, physiology and neuroendocrinology subsequent to selective inter- and intra-strain breeding homozygous rats with well characterized behavioral and cardiovascular phenotypes. After accurately describing differences between homozygous salt avid/high blood pressure and salt avoiding/low blood pressure rats in binding of aldosterone and expression of angiotensinogen messenger RNA in brain, subgroups of the segregating F2 descendants of these inbred strains will be selected, based on extremes of slat appetite and blood pressure, for a genetic analysis of linkage among these traits. Covariation between selected salt appetite or blood pressure phenotypes and neuroendocrine measures in the F2 population will provide evidence for genetic linkage, whereas independent assortment of phenotypes will support an interpretation of no genetic linkage. Additional experiments will examine strain differences in the development of aldosterone binding and Ao gene expression in the brain, relative to the development of salt appetite and blood pressure. The development analyses can provide support for neuroendocrine mediation of either the behavioral or cardiovascular phenotype by evaluating the temporal relationship between changes in aldosterone binding or Ao gene expression and the traits to which they are linked. The mental health relevance of the proposed research derives from the insights that it will provide genetic and development influences on motivated behavior, circulatory control and possible neuroendocrine mechanisms through which these influences are mediated.

拟议中的实验将研究大脑与 醛固酮结合血管紧张素原基因表达调控血管紧张素转换酶 模范动机行为(食盐消费)和监管 生理过程(循环)。基因对这些基因的影响 将通过分析表型变异来研究过程 选择性手术后的行为、生理和神经内分泌学 品系间和品系内培育特性良好的纯合子大鼠 行为和心血管表型。在准确地描述了 纯合子盐嗜好/高血压与食盐的差异 避免/低血压大鼠结合醛固酮和 血管紧张素原信使RNA在脑内的表达 将选择这些近交系的分离F2后代， 根据极端的食欲和血压，对于基因 这些性状之间的连锁分析。所选对象之间的协变 食盐或血压表型与神经内分泌指标 将为遗传连锁提供证据，而 独立的表型分类将支持对 没有遗传关联。 更多的实验将检查应变差异在 脑内醛固酮结合和ao基因表达的发展， 相对食盐的发育和血压。这个 发育分析可为神经内分泌调节提供支持 无论是行为表型还是心血管表型 醛固酮结合或ao基因变化之间的时间关系 表达以及它们与之相关的特征。 这项拟议研究的心理健康相关性源于 它将对以下方面提供遗传和发育影响的见解 动机行为、循环控制和可能的神经内分泌 这些影响被调节的机制。