THYROID HORMONE CONTROL OF BEHAVIOR & GENE EXPRESSION

甲状腺激素(T3、T4)起关键作用，但只起到部分作用 理解在发展和维护正常生活中的作用 外周和中枢神经系统功能、行为和 学习。智力低下、学习障碍和神经病 精神异常包括精神错乱，痴呆症， 精神病、妄想症和抑郁症 据报道患有甲亢或甲减。甲状腺功能不全 宫内生活中的荷尔蒙是引起 先天性甲状腺功能减退症，这是精神疾病的一个原因 发育迟缓、学习障碍、运动障碍、耳聋和 失明。先天性甲状腺功能减退综合征1例 在5000个新生儿中。认知、神经学和精神病学 表现可能与甲状腺介导的改变有关。 发展大脑基因表达。对于我们对 人类疾病的病理生理学和治疗 先天性甲状腺功能减退症模型是必不可少的。 本拟议系列研究的总体目的是 利用跨学科的方法来确定 近交系小鼠智力低下动物模型的建立 先天性甲状腺功能减退小鼠并利用该模型阐明 甲状腺激素对特定脑基因的调控机制 表情。此模型可能会帮助我们更多地了解 行为的分子生物学基础，治疗，病因， 和精神发育迟滞的底物以及首字母和 甲状腺激素对发育中的大脑的普遍影响。 具体目标是：1)进一步表征行为， HYT/HYT甲状腺功能减退症患者存在的学习差异 小鼠胚胎、新生儿和青壮年相对于正常小鼠 后代。2)定量检测包括IGF-1在内的多个小鼠mRNAs 和EGF，它们受甲状腺激素的调节 胎鼠甲状腺发病后的宫内期 功能(妊娠14至19天)。3)在大脑中进行定量 皮质和甲状腺激素调节脑的特征 正常和HYT/HYT小鼠的mRNAs。4)尝试本地化和 量化这些甲状腺激素调节的大脑皮层mRNAs 在大脑皮质III-IV层的特定细胞群中进行原位观察 杂交。5)将行为、神经解剖学、 以及分子生物学的结果。

Thyroid hormones (T3, T4) play a critical but only partially understood role in the development and maintenance of normal peripheral and central nervous system function, behavior, and learning. Mental retardation, learning disability, and neurological and psychiatric abnormalities including delirium, dementia, psychosis, and paranoid ideation, and depression have been reported with hyper or hypo-thyroidism. Deficiency of thyroid hormone during intrauterine life underlies the syndrome of congenital hypothyroidism, which is a cause of mental retardation, impaired learning, motor disability, deafness, and blindness. The syndrome of congenital hypothyroidism occurs in 1 in 5000 births. The cognitive, neurological and psychiatric manifestations may be related to thyroid mediated changes in developing brain gene expression. For our understanding of the pathophysiology and treatment of the human condition, an animal model of congenital hypothyroidism is essential. The general purpose of the present proposed series of studies is to utilize an interdisciplinary approach to determine the utility of an inbred mouse animal model of mental retardation, the hyt-hyt congenitally hypothyroid mouse and to use this model to elucidate the mechanism of thyroid hormone control of specific brain gene expression. This model may help us learn more about the molecular biological basis of behavior, the treatment, etiology, and substrate of mental retardation as well as the initial and pervasive effects of thyroid hormones on the developing brain. The specific aims are: 1) To further characterize the behavioral, and learning differences that exist in the hyt/hyt hypothyroid mouse fetus, neonate and young adult relative to normal mouse offspring. 2) To quantitate several mouse mRNAs including IGF-1 and EGF which are regulated by thyroid hormones during the intrauterine period following the onset of fetal mouse thyroid function (14 to 19 days of gestation). 3) To quantitate in cerebral cortex and characterize the thyroid hormone regulated brain mRNAs in normal and hyt/hyt mice. 4) To try to localize and quantify these thyroid hormone regulated cerebral cortex mRNAs in specific cell groups in cerebral cortex layers III-IV by in situ hybridization. 5) To correlate the behavioral, neuroanatomical, and molecular biology results.