FETAL SWALLOWING--ONTOGENY AND REGULATION

胎儿吞咽——个体发育和调节

• 批准号: 2518299
• 负责人: Michael Glenn Ross
• 金额: $ 20.88万
• 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/2518299
• 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，与精氨酸加压素一致 （AVP）介导的抗利尿，是维持身体的基本系统 水量和张力。原发性致渴反应是通过 血浆或脑脊液高渗（OSM）和血管紧张素II (AII)作用于缺乏血脑屏障的特定大脑区域。 自发性胎儿吞咽发生在个体发育早期， 在羊水稳态、胎儿胃肠道 发育，也许还有胎儿的躯体生长和成熟。短期内， 系统性和中枢性致渴机制在 羊胎儿，因此可能会受到影响，也许在 怀孕我们假设：（1）胎儿对假定的致渴剂的反应 (OSM，所有）在最后三分之一的时间里急剧成熟（“开启”）。 妊娠，反映了整合神经机制的成熟，以及（2） 内分泌（AVP;心房钠尿肽家族， ANP）对OSM和AII致渴反应的调节与 脑区特异性AVP和ANP受体结合的开始 调节致渴反应。提出实验来表征 胎儿对全身和中枢OSM致渴反应的个体发生 和AII，AVP和ANP对致渴反应的调节， AVP、AMP和AII受体亚型的选择性作用。中央 将使用AII和OSM检查致渴反应 显微注射和选择脑核团的立体定位病变，以及 致渴反应的成熟和内分泌调节将是 与脑AII、AVP和AMP受体的个体发生性变化相关 约束力除了吞咽，其他神经行为 （皮层电，“呼吸”）活动，胎儿心血管 将监测所有受试者的参数和血浆内分泌反应。 问题研究这种生理和内分泌方法的结合， 选择性脑核团功能检查将提供重要的新信息 信息，在早熟物种，关于子宫内成熟 对子宫外液平衡至关重要的致渴机制。