TY - JOUR

T1 - Thyrotropin-releasing hormone induces Ca2+ increase in a subset of vagal nodose ganglion neurons

AU - Mamedova, Esmira

AU - Dmytriyeva, Oksana

AU - Rekling, Jens C.

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - 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 Ca2+ indicator (GECI), we show that TRH increases Ca2+ in a subset of NG neurons. TRH-induced Ca2+ 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 Ca2+ 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.

AB - 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 Ca2+ indicator (GECI), we show that TRH increases Ca2+ in a subset of NG neurons. TRH-induced Ca2+ 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 Ca2+ 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.

KW - Ca imaging

KW - Nodose ganglion

KW - Thyrotropin-releasing hormone

KW - TRH

KW - Vagus nerve

U2 - 10.1016/j.npep.2022.102261

DO - 10.1016/j.npep.2022.102261

M3 - Journal article

C2 - 35704969

AN - SCOPUS:85132233919

VL - 94

JO - Neuropeptides

JF - Neuropeptides

SN - 0143-4179

M1 - 102261

ER -