THYROID HORMONE CONTROL OF BEHAVIOR & GENE

甲状腺激素（T3，T4）发挥关键作用，但只是部分 在发展和维持正常 外周和中枢神经系统功能，行为， 学习 智力迟钝、学习障碍和神经系统疾病 精神异常包括谵妄痴呆 精神病、偏执狂和抑郁症 报告甲状腺功能亢进或减退。 甲状腺功能不全 激素在子宫内生活的基础综合征 先天性甲状腺功能减退症，这是一个原因， 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发生在1 在5000个出生。 认知、神经和精神 表现可能与甲状腺介导的变化有关， 发展大脑基因表达。 对我们理解 病理生理学和人类状况的治疗，动物 先天性甲状腺功能减退症的模型是必不可少的。 目前提出的一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 先天性甲状腺功能低下小鼠，并使用该模型来阐明 甲状腺激素调控脑特异性基因机制 表情 这个模型可以帮助我们更多地了解 行为的分子生物学基础，治疗，病因， 和基质的精神发育迟滞，以及最初的， 甲状腺激素对大脑发育的广泛影响。 具体目的是：1）进一步表征行为， 和存在于hyt/hyt甲状腺功能减退症中的学习差异 相对于正常小鼠的小鼠胎儿、新生儿和青年 后代 2)为了定量几种小鼠mRNA，包括IGF-1 EGF是由甲状腺激素调节的。 胎鼠甲状腺发生后的宫内期 功能（妊娠14至19天）。 3)在大脑中定量 皮质和表征甲状腺激素调节的大脑 正常和hyt/hyt小鼠中的mRNA。 4)尝试本地化， 定量这些甲状腺激素调节的大脑皮层mRNA 在大脑皮层III-IV层的特定细胞群中， 杂交方法 5)为了将行为神经解剖学， 和分子生物学结果。

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.