NEUROPHYSIOLOGY OF THE HYPOTHYROID OVINE FETUS

甲状腺功能减退症绵羊胎儿的神经生理学

• 批准号: 3319781
• 负责人: GAIL E RICHARDS
• 金额: $ 2.47万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319781
• 关键词: 5 hydroxytryptophan; apomorphine; auditory stimulus; brain; cerebrospinal fluid; clonidine; developmental neurobiology; dopamine; electrodes; evoked potentials; gas chromatography mass spectrometry; gestational age; high performance liquid chromatography; hypothyroidism; neurons; neurophysiology; neurotransmitters; norepinephrine; prenatal growth disorder; prolactin; radioimmunoassay; respiratory gas analyzer; sensorimotor system; serotonin; sheep; thyroid hormones; thyroidectomy

Central nervous system (CNS) dysfunction continues to be a problem in infants with congenital primary hypothyroidism in spite of the advances made to allow early diagnosis and treatment through neonatal screening programs. Many of these CNS abnormalities may be due to the effect of hypothyroidism in intrauterine life. The long term objective of this study is to determine the effect of fetal thyroidectomy on some markers of brain maturation and function using the ovine fetus as the experimental model. The specific aims of the study are to prove that (1) thyroidectomy in the ovine fetus causes significant delay in the maturational pattern of the neurotransmitters norepinephrine (NE), dopamine (DA), and serotonin (5HT) in specific brain areas, and auditory and somatosensory evoked responses (ER). (2) Replacement therapy with thyroid hormones allows the normal maturational progress of NE, DA 5HT and ER in these areas to resume. (3) If therapy is delayed past a "critical time period," the normal maturation of NE, DA, 5HT and ER is permanently arrested. (4) The changes in NE, DA and 5HT caused by ovine fetal thyroidectomy cause plasma concentrations of growth hormone (GH) and prolactin (PRL) to be unresponsive to the NE receptor agonist clonidine the DA receptor agonist apomorphine, and the 5HT precursor 5 hydroxytryptophan (5HTP). To achieve these aims, ovine fetuses will undergo thyroidectomy at 85 days gestation. Control fetuses will undergo sham thyroidectomy. To accomplish Aim 1: NE, DA and 5HT in cerebrospinal fluid (CSF) and EF will be measured at set intervals in thyroidectomy and control fetuses. NE, DA and 5HT will also be measured in specific brain areas at the conclusion of the experiment. Aim 2: thyroid hormone replacement therapy will be given to thyroidectomized fetuses beginning at different intervals after thyroidectomy NE, DA and 5HT in CSF and ER will be measured at set intervals for the remainder of gestation. At the conclusion of the experiment, NE, DA and 5HT will be measured in specific brain areas. Aim 3: thyroidectomized fetuses will be studied at more frequent intervals for a limited segment of gestation with measurement of NE, DA and 5HT in CSF and in specific brain areas at the end of the experiment. Aim 4: the response of plasma GH and PRL to clonidine, apomorphine and 5HTP in thyroidectomized and control fetuses will be tested. The results of this study will more clearly define the mechanism by which hypothyroidism interferes with CNS function during fetal development.

中枢神经系统（CNS）功能障碍仍然是一个问题， 先天性原发性甲状腺功能减退症的婴儿， 通过新生儿筛查进行早期诊断和治疗 程序. 许多中枢神经系统异常可能是由于 宫内生活中甲状腺功能减退。 本研究的长期目标是确定胎儿的影响， 甲状腺切除术对脑成熟和功能的一些标志物的影响， 以绵羊胎儿为实验模型。 研究的具体目标是 证明：（1）羊胎甲状腺切除术导致显著延迟 在神经递质去甲肾上腺素（NE）的成熟模式中， 多巴胺（DA）和5-羟色胺（5-HT）在特定的大脑区域，和听觉 和体感诱发反应（ER）。 (2)替代治疗 甲状腺激素允许NE、DA 5 HT和 在这些方面，恢复。 (3)如果治疗延迟超过“临界 在一段时间内，”NE、DA、5 HT和ER的正常成熟是永久性的， 被捕了 (4)绵羊胎仔注射后NE、DA和5-HT的变化 甲状腺切除术引起生长激素（GH）的血浆浓度， 催乳素（PRL）对NE受体激动剂可乐定无反应， DA受体激动剂阿扑吗啡和5-HT前体5-羟色氨酸 （5HTP）。 为了达到这些目的，绵羊胎儿将在85天时接受甲状腺切除术 怀孕 对照胎仔将接受假甲状腺切除术。 完成 目的1：测定脑脊液（CSF）中NE、DA、5-HT及EF 在甲状腺切除术和对照胎儿中以设定的时间间隔。 NE、DA和5 HT将 也可以在特定的大脑区域进行测量， 实验 目的2：甲状腺激素替代治疗将给予 甲状腺切除后不同时间开始的胎仔 将在设定时间点测量CSF和ER中的NE、DA和5 HT 妊娠期剩余时间的间隔。 结束时 实验中，将在特定脑区测量NE、DA和5 HT。 目的 3：将以更频繁的时间间隔研究甲状腺切除胎仔， 有限妊娠期脑脊液NE、DA和5-HT测定 在实验结束时，在特定的大脑区域。 目标4： 可乐定、阿朴吗啡和5-羟色胺对垂体后叶素的反应 将对甲状腺切除的和对照的胎儿进行测试。 这项研究的结果将更清楚地界定机制， 甲状腺功能减退在胎儿发育期间干扰CNS功能。