# Corticotropin‐releasing factor type 1 receptors in the rat nodose ganglion are involved in the transduction of stress‐induced visceral sensory signals to the brain

## TL;DR

The study shows that CRF and its receptor CRF1 in the nodose ganglion help transmit stress-related signals from the colon to the brain.

## Contribution

The study identifies a novel role of the CRF/CRF1 system in relaying visceral sensory signals via the nodose ganglion during stress.

## Key findings

- CRF1 is expressed in the nodose ganglion and colonic sensory neurons.
- CRF and stress increase pCREB expression in the nodose ganglion.
- CRF1 antagonists reduce stress-induced signaling in the nodose ganglion.

## Abstract

Corticotropin‐releasing factor (CRF) plays roles in stress‐related responses through its type 1 (CRF1) and type 2 receptors. Both CRF and CRF1 are expressed in the rat colon. Peripheral CRF administration and various stressors increase colonic motility and defecation. Stress induces CRF release in the colon, suggesting CRF may mediate stress‐related responses of the colon. The vagal nodose ganglion (NG) transduces visceral information, including colonic sensation, to the brain. However, it remains unclear whether the CRF/CRF1 system is involved in vagal afferent functions. This study, therefore, aimed to clarify the involvement of the CRF/CRF1 system in relaying visceral sensory information to the brain and the effect of stress exposure on vagal nerve function. The experiments were conducted in male rats. First, CRF1‐like immunoreactivity (CRF1‐LI) was characterized in the NG. Second, the effects of vagotomy on CRF1‐LI in the NG, intraperitoneally administered CRF‐induced fecal output, and c‐Fos expression in the nucleus tractus solitarius (NTS) were evaluated. Subsequently, a fast blue retrograde tracer was microinjected into the proximal colon. Finally, we analyzed CRF‐ or stress‐induced phosphorylation of cyclic AMP‐response element‐binding protein (pCREB) in the NG. CRF1 mRNA and CRF1‐LI were detected, and CRF1‐LI accumulated on the proximal side of the ligated region of the nerve trunk, and CRF1‐LI was detected in most cholinergic neurons. CRF1 siRNA suppressed the expression of CRF1‐LI in the NG. Subdiaphragmatic vagotomy decreased the number of CRF1‐positive cells in the NG while it did not affect CRF‐induced fecal output. CRF‐induced c‐Fos expression in the NTS was suppressed by vagotomy. A neuronal tracing study showed that approximately half of CRF1‐positive cells expressed fast blue in the NG. Intraperitoneal CRF, a selective CRF1 agonist, or immobilization stress induced pCREB expression and increases in CRF1‐positive cells in the NG. In contrast, a CRF1 antagonist reduced the immobilization‐induced increase in the expression of pCREB in the NG. These results suggest that the CRF/CRF1 system is involved in the signal transduction of colonic sensory information to the central nervous system via the NG.

Corticotropin‐releasing factor (CRF) and its type 1 receptor (CRF1) are expressed in the rat colon. The vagal nodose ganglion transmits visceral information to the brain; but whether the CRF/CRF1 system is involved in vagal afferent function remains unknown. This study confirmed the role of CRF/CRF1 in mediating colonic sensory information to the central nervous system via the nodose ganglion in Wistar rats.