RUI: Physiological and Biochemical Interactions of Thyroid Hormones with GABAa Receptors of the CNS

约瑟夫·V·马丁IBN 98-09943该提案的目标是阐明甲状腺激素如何影响成年哺乳动物的大脑。在生长和发育过程中，来自甲状腺的激素进入多种细胞类型(包括脑细胞)，改变蛋白质的合成。成年后，甲状腺激素进入许多组织的细胞，而不是进入大脑，细胞代谢率会加快。然而，成年后甲状腺腺病的一些潜在的最令人衰弱的并发症是由于神经疾病，从焦虑和睡眠问题到癫痫发作或昏迷。初步证据表明，甲状腺激素与大脑GABAA受体结合并影响其功能。这些位于神经细胞膜外的蛋白质负责主要抑制性神经递质(神经元之间的局部化学信使)--伽马氨基丁酸或GABA的细胞效应。进一步的初步工作表明，根据脑电(EEG)的测量，甲状腺激素对整个脑电活动的影响。实验将在大鼠身上进行，以确定甲状腺激素对GABAA受体结合和随后的细胞反应的影响类型。少量的甲状腺激素将被直接注射到选定的大脑区域，以确定调节甲状腺激素对脑电和体温调节影响的部位的敏感性。这些研究的结果将阐明甲状腺激素的大脑作用的生物学意义，与其他组织中甲状腺激素的典型作用相比，它更类似于神经递质的作用。

Joseph V. Martin IBN 98-09943 The goal of the proposal is to clarify how thyroid hormones influence the adult mammalian brain. During growth and development, hormones from the thyroid gland enter many cell types (including brain cells) and alter protein synthesis. In adulthood, the cellular metabolic rate is accelerated by thyroid hormones entering cells of many tissues, but not in the brain. However, some of the potentially most debilitating complications of thyroid glandular disease in adulthood are due to neurological disorders, ranging from anxiety and sleep problems to seizures or coma. The preliminary evidence demonstrates that thyroid hormones bind to and influence the function of brain GABAa receptors. These proteins on the outside of neuronal membranes are responsible for cellular effects of the major inhibitory neurotransmitter (local chemical messenger between neurons), gamma-aminobutyric acid or GABA. Further preliminary work indicates effects of thyroid hormones on the whole brain electrical activity, as measured in the electroencephalogram (EEG). Experiments will be performed in rats to determine the types of effects that thyroid hormones have on the GABAa receptor binding and the subsequent cellular response. Small amounts of thyroid hormones will be injected directly into selected brain areas to ascertain the sensitivity of the sites in mediating thyroid hormonal effects on EEG and temperature regulation. The results of these studies will elucidate the biological significance of a brain action of thyroid hormones that more closely resembles the action of a neurotransmitter than the typical action of thyroid hormones in other tissues.