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

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Abstract
Corticotropin‐releasing factor (CRF) plays roles in stress‐related responses through its type 1 (CRF 1 ) and type 2 receptors. Both CRF and CRF 1 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/CRF 1 system is involved in vagal afferent functions. This study, therefore, aimed to clarify the involvement of the CRF/CRF 1 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, CRF 1 ‐like immunoreactivity (CRF 1 ‐LI) was characterized in the NG. Second, the effects of vagotomy on CRF 1 ‐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. CRF 1 mRNA and CRF 1 ‐LI were detected, and CRF 1 ‐LI accumulated on the proximal side of the ligated region of the nerve trunk, and CRF 1 ‐LI was detected in most cholinergic neurons. CRF 1 siRNA suppressed the expression of CRF 1 ‐LI in the NG. Subdiaphragmatic vagotomy decreased the number of CRF 1 ‐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 CRF 1 ‐positive cells expressed fast blue in the NG. Intraperitoneal CRF, a selective CRF 1 agonist, or immobilization stress induced pCREB expression and increases in CRF 1 ‐positive cells in the NG. In contrast, a CRF 1 antagonist reduced the immobilization‐induced increase in the expression of pCREB in the NG. These results suggest that the CRF/CRF 1 system is involved in the signal transduction of colonic sensory information to the central nervous system via the NG.
Funding Information
  • Japan Society for the Promotion of Science (JP23K07023)

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