Department of Neuroscience, University of Copenhagen, Panum - 24.4, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Neuropeptides. 2022 Aug;94:102261. doi: 10.1016/j.npep.2022.102261. Epub 2022 Jun 3.
Thyrotropin-releasing hormone (TRH) plays a central role in metabolic homeostasis, and single-cell sequencing has recently demonstrated that vagal sensory neurons in the nodose ganglion express thyrotropin-releasing hormone receptor 1 (TRHR1). Here, in situ hybridization validated the presence of TRHR1 in nodose ganglion (NG) neurons and immunohistochemistry showed that the receptor is expressed at the protein level. However, it has yet to be demonstrated whether TRHR1 is functionally active in NG neurons. Using NG explants transduced with a genetically encoded Ca indicator (GECI), we show that TRH increases Ca in a subset of NG neurons. TRH-induced Ca transients were briefer compared to those induced by CCK-8, 2-Me-5-HT and ATP. Blocking Na channels with TTX or Na substitution did not affect the TRH-induced Ca increase, but blocking Gq signaling with YM-254890 abolished the TRH-induced response. Field potential recordings from the vagus nerve in vitro showed an increase in response to TRH, suggesting that TRH signaling produces action potentials in NG neurons. These observations indicate that TRH activates a small group of NG neurons, involving Gq pathways, and we hypothesize that these neurons may play a role in gut-brain signaling.
促甲状腺素释放激素（TRH）在代谢稳态中发挥核心作用，单细胞测序最近表明，迷走神经感觉神经元在结状神经节中表达促甲状腺素释放激素受体 1（TRHR1）。在这里，原位杂交验证了结状神经节（NG）神经元中存在 TRHR1，免疫组织化学显示受体在蛋白质水平表达。然而，尚未证明 TRHR1 在 NG 神经元中是否具有功能活性。使用转导有遗传编码 Ca 指示剂（GECI）的 NG 外植体，我们表明 TRH 增加了一部分 NG 神经元中的 Ca。与 CCK-8、2-Me-5-HT 和 ATP 诱导的 Ca 瞬时相比，TRH 诱导的 Ca 瞬变更短暂。用 TTX 或 Na 替代阻断 Na 通道不会影响 TRH 诱导的 Ca 增加，但用 YM-254890 阻断 Gq 信号会使 TRH 诱导的反应消失。在体外迷走神经的场电位记录显示对 TRH 的反应增加，这表明 TRH 信号在 NG 神经元中产生动作电位。这些观察结果表明，TRH 激活一小群涉及 Gq 途径的 NG 神经元，我们假设这些神经元可能在肠道-大脑信号传递中发挥作用。
