Glucagon-Like Peptide-1 Targets in the Human Nodose Ganglion

Given the rapidly expanding clinical use of glucagon-like peptide-1 receptor (GLP1R) agonists-well-known for their antidiabetic and antiobesity effects-it is increasingly important to understand the precise distribution of GLP1R expression in the human body, as this knowledge is crucial for elucidating both their therapeutic effects and side effects. In this study, we investigated Glp1r mRNA expression in the human nodose ganglion, a key sensory relay between the periphery and the brain. We analyzed postmortem paraffin-embedded nodose ganglia sections from 10 human donors, using RNAscope analysis. We found that optimal tissue required fixation times under 48 h and postmortem intervals of approximately 10 h or less. Ultimately, nine nodose ganglia from six donors met quality standards for analysis. Using multiplex RNAscope, we detected moderate to high levels of Glp1r expression in approximately 7% of all nodose neurons, with no clear differences between sides, sex, or age. The proportion of neurons with low Glp1r expression rose to nearly 28%. Notably, Glp1r expression was also observed in nonneuronal cells within the perineurium, epineurium, and fascicles of the human vagus nerve. As a point of comparison, we also examined Glp1r expression in mice, where 17.9%-29.1% of nodose neurons were positive, with slightly higher expression on the right side. In mice, Glp1r expression was strictly neuronal. Overall, our findings demonstrate that the human nodose ganglion is a potential target for GLP1R-based therapeutics and reveal species similarities and differences in Glp1r expression between humans and mice.