BRAIN PEPTIDES AND THE REGULATION OF CIRCADIAN RHYTHMS

脑肽和昼夜节律的调节

• 批准号: 3078074
• 负责人: William J Schwartz
• 金额: $ 5.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-01-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3078074
• 关键词: action potentials; autoradiography; biological clocks; circadian rhythms; embryo /fetus; neural information processing; pharmacology; radioimmunoassay; suprachiasmatic nucleus; tetrodotoxin; vasopressins

The objective of my research program continues to focus on the neural regulation of circadian rhythms by the suprachiasmatic nuclei (SCN) of the hypothalamus. The first set of experiments will analyze the relationship between energy metabolism and function in the SCN using the 2-deoxy-D-(14C)glucose (DG) autoradiographic method. Fetal SCN energy metabolism is rhythmic in utero, before either SCN synaptogenesis or the circadian rhythm of SCN impulse activity becomes apparent post-natally. Experiments will test the hypothesis that the generation & propagation of action potentials by the SCN is not an integral part of the actual circadian timing device. Mini-osmotic pumps will locally perfuse the SCN with one millionth M tetrodotoxin (TTX) at 0.5 Mul/hr for 14 days; free-running rhythmic drinking behavior of blinded rats will be monitored before, during and after infusion of the toxin. This paradigm will be used to (a) uncouple the circadian clock in the SCN from both its afferents and efferents, (b) determine a dose-response relationship for TTX infusion, (c) demonstrate topographical specificity of the agent, and (d) quantitate the resulting rhythm of SCN energy metabolism. The second set of experiments will use the DG method to determine how the maternal circadian system coordinates the timing of the developing fetal clock. Studies for the coming year include (a) maternal SCN ablation at later gestational ages, (b) maternal oophorectomy, and (c) evaluation of non-endocrine behavioral mechanisms using food restriction, shifting of mealtimes, and continuous intravenous hyperalimentation regimes. The third set of experiments will investigate the physiological role for the circadian vasopressin rhythm in cerebrospinal fluid (CSF). Preliminary data suggest that the circadian rhythm of brain temperature is severely disturbed in homozygous Brattleboro rats. Further characterization of this abnormality will lead to experiments to (a) abolish the normal temperature rhythms of Long-Evans rats by intracerebroventricular administration of vasopressin antibody or antagonist, and (b) restore temperature rhythmicity in Brattleboro homozygotes by artificial simulation of normal CSF vasopressin rhythms or by transplantation of the fetal SCN. Vasopressin is measured by a sensitive and specific radioimmunoassay.

我的研究计划的目标仍然集中在神经上 视交叉上核（SCN）对昼夜节律的调节 下丘脑 第一组实验将分析能量与 使用2-脱氧-D-（14 C）葡萄糖（DG）在SCN中的代谢和功能 放射自显影法 胎儿SCN能量代谢在子宫内是有节律的， 在SCN突触发生或SCN脉冲的昼夜节律之前 活动在出生后变得明显。 实验将测试 假设动作电位的产生和传播是由 SCN不是实际昼夜节律计时装置的组成部分。 微型渗透泵将局部灌注SCN百万分之一M 河豚毒素（TTX），0.5穆尔/小时，持续14天;自由节律 将在之前、期间和之后监测盲态大鼠的饮水行为。 注射了毒素之后 这个范例将用于（a）分离 SCN中来自其传入和传出的昼夜节律钟，（B） 确定TTX输注的剂量-反应关系，（c）证明 所述试剂的地形特异性，和（d）定量所得到的 SCN能量代谢节律。 第二组实验将使用DG方法来确定 母亲的昼夜节律系统协调胎儿发育的时间 时钟 未来一年的研究包括：（a）母体SCN消融， 晚孕龄，（B）母体卵巢切除术，和（c）评估 非内分泌行为机制，使用食物限制， 进餐时间和持续静脉高营养方案。 第三组实验将研究 脑脊髓液（CSF）中加压素的昼夜节律。 初步 数据表明，大脑温度的昼夜节律严重 在纯合子Brattleboro大鼠中受到干扰。 对此的进一步描述 异常将导致实验（a）废除正常温度 Long-Evans大鼠通过脑室内施用 加压素抗体或拮抗剂，和（B）恢复温度节律性 在Brattleboro纯合子中通过人工模拟正常CSF 加压素节律或通过移植胎儿SCN。 加压素 通过灵敏和特异的放射免疫测定法测量。

项目成果

Local cerebral glucose utilization in the homozygous Brattleboro rat.

纯合布拉特尔伯勒大鼠的局部脑葡萄糖利用。

• DOI: 10.1016/0304-3940(85)90159-4
• 发表时间: 1985
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Schwartz,WJ;Crosby,G
• 通讯作者: Crosby,G