EFFECTS OF THYROID HORMONES ON BRAIN SYNAPSES

甲状腺激素对大脑突触的影响

• 批准号: 3406184
• 负责人: GEORGE A MASON
• 金额: $ 7.15万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406184
• 关键词: antidepressants; brain stem; cerebral cortex; cerebrum; corpus striatum; gamma aminobutyrate; hyperthyroidism; hypothalamus; hypothyroidism; neurochemistry; neurotransmitter biosynthesis; radioassay; serotonin; synapses; synaptosomes; thyroid hormones; triiodothyronine

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.

虽然甲状腺疾病的行为影响早已被认识到， 直到最近，很少有明确的证据表明， 这些行动。 现在已经证明甲状腺激素被摄取 并在大脑的突触间部分代谢， 甲状腺状态改变神经递质的合成和周转， 几种神经递质受体。 此外，临床医生 使用甲状腺激素来增强 抗抑郁药物，也影响突触过程。 这些发现 甲状腺激素在突触中的功能作用。 关于tehse 考虑到这些因素，我们进行了一项试验性研究， 甲状腺激素对多种神经递质的摄取。 我们 观察到在大鼠大脑皮质T3和T4的新鲜匀浆中， 抑制GABA和5-HT的神经元摄取，但对NE、DA、天冬氨酸 asid或胆碱。 我们正在提交一项建议，以继续并扩大关于 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GABA和5-HT摄取的影响 从大脑皮层和其他大脑区域的突触体，研究 慢性甲状腺功能亢进症和甲状腺功能减退症对 神经递质摄取，检查甲状腺激素的影响， 甲状腺状态对GABA和5-HT受体的影响。 我们还计划调查 甲状腺激素在突触水平的相互作用， 抗抑郁药 由于一些国家之间的相似之处， 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，我们将研究rT 3是否被 突触体（如T4和T3），甲状腺激素是否在突触体中释放， 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。