EFFECTS OF THYROID HORMONES ON BRAIN SYNAPSES

尽管人们很早就认识到了甲状腺疾病的行为影响， 直到最近，几乎没有明确的证据表明脑神经基础 这些行动。现在已经证明甲状腺激素被吸收了。 并在大脑的突触部分代谢，这种变化 甲状腺状态改变神经递质合成和周转及其状态 几种类型的神经递质受体。此外，临床医生 曾使用甲状腺激素来加强对 抗抑郁药物，这也会影响突触过程。这些发现 提示甲状腺激素在突触中的功能作用。与Tehse一起 考虑到这些因素，我们进行了一项初步研究 甲状腺激素对多种神经递质的摄取。我们 在新鲜大鼠大脑皮层T3和T4匀浆中观察到 抑制GABA和5-羟色胺的摄取，但不抑制NE、DA、天冬氨酸的摄取 阿西德或胆碱。 我们正在提交一份提案，以继续和扩大这项关于 甲状腺激素对神经递质摄取和其他突触的影响 流程。主要目的是进一步描述 甲状腺激素对匀浆和纯品中GABA和5-羟色胺摄取的影响 大脑皮层和其他脑区的突触体，以研究 慢性甲状腺功能亢进症和甲状腺功能减退症对心脏功能的影响 神经递质摄取，以检查甲状腺激素和 甲状腺对GABA和5-羟色胺受体的影响。我们还计划调查 甲状腺激素和甲状腺激素在突触水平的交互作用 抗抑郁药。因为其中的一些相似之处 甲状腺激素和芳香族化合物的结构和生理特性 酸性神经递质，我们将调查rt3是否被 突触体(如T4和T3)，甲状腺激素是否在 已证实的神经递质的方式，以及甲状腺激素是否与 突触体膜上的受体。

Although behavioral effects of thyroid disorders have long been recognized, until recently there has been little clear evidence of a neuronal basis for these actions. It has now been shown that thyroid hormones are taken up and metabolized in the synaptosmal fraction of brain and that changes in thyroid state alter neurotransmitter synthesis and turnover and the status of several types of neurotransmitter receptors. In addition, clinicians have used thyroid hormones to potentiate the therapeutic effects of antidepressant drugs, which also effect synaptic processes. These findings suggst a functional role of thyroid hormones at the synapse. With tehse considerations in mind, we conducted a pilot study of the effects of thyroid hormones on the uptake of a variety of neurotransmitters. We observed that in fresh homogenates of rat cerebral cortex T3 and T4 inhibited the nuronal uptake of GABA and 5-HT but not of NE, DA, aspartic asid or choline. We are submitting a proposal to continue and expand this work on the effects of thyroid hormones on neurotransmitter uptake and other synaptic processes. The major aims are to further characterize the effects of thyroid hormones on GABA and 5-HT uptake in homogenates and purified synaptosomes from cerebral cortex and other brain regions, to investigate the effects of chronic hyperthyroidism and hypothyroidism on neurotransmitter uptake, to examine the effects of thyroid hormones and thyroid status on GABA and 5-HT receptors. We also plan to investigate the interactive effects at the synaptic level of thyroid hormones and antidepressant drugs. Because of similarities between some of the structural and physiological properties of thyroid hormones and aromatic acid neurotransmitters, we will investigate whether rT3 is taken up by synaptosomes (like T4 and T3), whether thyroid hormones are released in the manner of proven neurotransmitters, and whether thyroid hormones bind to receptors on synaptosomal membranes.