FETAL SWALLOWING--ONTOGENY AND REGULATION

胎儿吞咽——个体发育和调节

• 批准号: 2142903
• 负责人: Michael Glenn Ross
• 金额: $ 17.72万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2142903
• 关键词: angiotensin II; arginine vasopressin; atrial natriuretic peptide; body fluid osmolarity; body water; cerebral cortex; circadian rhythms; electromyography; embryo /fetus; gestational age; homeostasis; microinjections; peripheral nervous system; physiology; radioimmunoassay; receptor binding; sheep; stereotaxic techniques; stimulus /response; swallowing; thirst regulatory center

Thirst-mediated drinking behavior, in concert with arginine vasopressin (AVP)-mediated antidiuresis, are the fundamental systems maintaining body water volume and tonicity. Primary dipsogenic responses are mediated via plasma or cerebrospinal fluid hyperosmolality (OSM) and angiotensin II (AII), acting at select cerebral regions lacking a blood-brain barrier. Spontaneous fetal swallowing occurs early during ontogeny and has important roles in amniotic fluid homeostasis, fetal gastrointestinal development, and perhaps fetal somatic growth and maturation. Near term, both systemic and central dipsogenic mechanisms are functional in the ovine fetus, and thus are likely influenced and perhaps imprinted during gestation. We hypothesize: (1) Fetal responses to putative dipsogens (OSM, AII) mature ("switch-on") acutely during the last third of gestation, reflecting maturation of integrated neural mechanisms, and (2) The development of endocrine (AVP; atrial natriuretic peptide family, ANP) modulation of OSM and AII dipsogenic responses is coincident with the onset of specific AVP and ANP receptor binding in cerebral regions regulating dipsogenic responses. Experiments are proposed to characterize the ontogeny of fetal dipsogenic responses to systemic and central OSM and AII, the modulation of dipsogenic responses by AVP and ANP, and the selective action of AVP, AMP and AII receptor subtypes. Central dipsogenic responses will be examined with both AII and OSM microinjections and stereotaxic lesions of select cerebral nuclei, and the maturation and endocrine modulation of dipsogenic responses will be correlated with ontogenic changes in cerebral AII, AVP and AMP receptor binding. In addition to swallowing, other neurobehavioral (electrocortical, "breathing") activities, fetal cardiovascular parameters and plasma endocrine responses will be monitored in all studies. This combination of physiologic and endocrine approaches and the examination of select cerebral nuclei function will provide important new information, in a precocial species, concerning the in utero maturation of dipsogenic mechanisms essential for extrauterine fluid homeostasis.

口渴介导的饮酒行为，与精氨酸加压素协同作用 促肾上腺皮质激素(AVP)介导的抗利尿是维持机体的基本系统 水的体积和色调。引起糖尿病的原发反应是通过 血浆或脑脊液高渗与血管紧张素II (Aii)，作用于缺乏血脑屏障的特定大脑区域。 自发的胎儿吞咽发生在个体发育的早期， 羊水动态平衡、胎儿胃肠道的重要作用 发育，也许还有胎儿的躯体生长和成熟。近期， 全身性和中枢性糖尿病的发生机制在 绵羊胎儿，因此可能受到影响，可能在 怀孕了。我们假设：(1)胎儿对可能的双酚类药物的反应 (OSM，AII)在最后三分之一迅速成熟(“开启”) 妊娠，反映集成神经机制的成熟，以及(2) 内分泌(AVP；心钠素家族， ANP)对OSM和AII糖尿病反应的调制与 脑区特异性AVP和ANP受体结合的开始 调节生发糖尿病的反应。我们建议进行实验来表征 全身性和中枢性OSM致胎儿糖尿病反应的个体发育 AII，AVP和ANP对致糖尿病反应的调节，以及 AVP、AMP和AII受体亚型的选择性作用。中环 将用AII和OSM检查引起糖尿病的反应 选定大脑核团的显微注射和立体定向术，以及 致糖尿病反应的成熟和内分泌调节将是 脑组织AII、AVP和AMP受体与个体发生变化的关系 有约束力的。除了吞咽，其他神经行为 (大脑皮层，“呼吸”)活动，胎儿心血管 将监测所有患者的参数和血浆内分泌反应 学习。这种生理和内分泌方法的结合，以及 对选定大脑核团功能的检查将提供重要的新 早熟物种中有关子宫内成熟的信息 对于宫外液的动态平衡至关重要的致病机制。