Vaidya V A, Castro M E, Pei Q, Sprakes M E, Grahame-Smith D G
University Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Woodstock Road, OX2 6HE, Oxford, UK.
Neuropharmacology. 2001;40(1):48-56. doi: 10.1016/s0028-3908(00)00094-0.
The aim of the present study was to determine the influence of thyroid hormone, T3, on the regulation of hippocampal BDNF expression by 5-HT receptor agonists. Chronic T3 administration prior to treatment with the 5-HT(1A) agonist, 8-OH-DPAT, significantly decreased BDNF mRNA in the dentate gyrus region of the hippocampus. Administration of 8-OH-DPAT did not alter hippocampal BDNF mRNA expression in naive, euthyroid rats. Pretreatment with the 5-HT(1A) antagonist, WAY 100635, completely blocked the 8-OH-DPAT-induced down-regulation of BDNF mRNA in chronic T3-treated rats. Acute T3 administration prior to 8-OH-DPAT treatment led to a small, but significant, decrease in hippocampal dentate gyrus BDNF mRNA. Acute or chronic administration of T3 did not alter the decrease in hippocampal BDNF mRNA induced by the 5-HT(2A/2C) receptor agonist, DOI. The influence of 8-OH-DPAT and DOI on hippocampal BDNF mRNA was also unaltered in rats rendered hypothyroid by propylthiouracil administration. Chronic T3 treatment or hypothyroidism did not influence the basal expression of hippocampal BDNF mRNA. The affinity and density of 5-HT(1A) receptors, and the hippocampal expression of 5-HT(1A) mRNA were also not influenced by chronic T3 treatment. The results of this study clearly demonstrate a powerful interaction between thyroid hormone and the 5-HT(1A) receptor in the regulation of hippocampal BDNF expression. Crosstalk between signal transduction cascades influenced by T3 and 5-HT(1A) receptors may mediate the synergistic effects of these systems on hippocampal BDNF expression.
本研究的目的是确定甲状腺激素T3对5-羟色胺（5-HT）受体激动剂调节海马脑源性神经营养因子（BDNF）表达的影响。在用5-HT（1A）激动剂8-OH-DPAT治疗前长期给予T3，可显著降低海马齿状回区域的BDNF mRNA水平。给予8-OH-DPAT不会改变正常甲状腺功能的未处理大鼠海马BDNF mRNA的表达。用5-HT（1A）拮抗剂WAY 100635预处理可完全阻断8-OH-DPAT诱导的长期T3处理大鼠BDNF mRNA的下调。在8-OH-DPAT治疗前急性给予T3可导致海马齿状回BDNF mRNA有小幅但显著的降低。急性或长期给予T3不会改变5-HT（2A/2C）受体激动剂DOI诱导的海马BDNF mRNA的降低。通过给予丙硫氧嘧啶使大鼠甲状腺功能减退，8-OH-DPAT和DOI对海马BDNF mRNA的影响也未改变。长期T3治疗或甲状腺功能减退不影响海马BDNF mRNA的基础表达。5-HT（1A）受体的亲和力和密度以及5-HT（1A）mRNA的海马表达也不受长期T3治疗的影响。本研究结果清楚地表明，甲状腺激素与5-HT（1A）受体在调节海马BDNF表达方面存在强大的相互作用。受T3和5-HT（1A）受体影响的信号转导级联之间的相互作用可能介导了这些系统对海马BDNF表达的协同作用。
