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Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species
Stephanie Fulton1, Charles C Horn2, Chuchu Zhang3
1UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Abstract:
Nausea is an uncomfortable sensation that accompanies many therapeutics, especially diabetes treatments involving glucagon-like peptide-1 receptor (GLP1R) agonists. Recent studies in mice have revealed that GLP1R-expressing neurons in the area postrema play critical roles in nausea. Here, we characterized a ligand-conjugated saporin that can efficiently ablate GLP1R+ cells from humans, mice, and the Suncus murinus, a small animal model capable of emesis. This new tool provides a strategy to manipulate specific neural pathways in the area postrema in the Suncus murinus and may help elucidate roles of area postrema GLP1R+ neurons in emesis during therapeutics involving GLP1R agonists.
Insights
Researchers developed a new tool to eliminate glucagon-like peptide-1 receptor (GLP1R)-expressing cells. This method helps study GLP1R neurons
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Nausea is a common side effect of therapeutics, particularly glucagon-like peptide-1 receptor (GLP1R) agonists used for diabetes.
- GLP1R-expressing neurons in the area postrema are implicated in nausea.
- Understanding these neural pathways is crucial for managing therapeutic side effects.
Purpose of the Study:
- To characterize a novel ligand-conjugated saporin for ablating GLP1R+ cells.
- To provide a tool for manipulating area postrema neural pathways in the Suncus murinus model.
- To facilitate research into the role of GLP1R+ neurons in emesis.
Main Methods:
- Development and characterization of a ligand-conjugated saporin.
- Testing the efficacy of the saporin in ablating GLP1R+ cells in human, mouse, and Suncus murinus models.
- Utilizing the Suncus murinus as a model for emesis studies.
Main Results:
- Successfully characterized a saporin conjugate that ablates GLP1R+ cells across species (human, mouse, Suncus murinus).
- Demonstrated the tool's potential for targeted neural pathway manipulation in the area postrema.
- Established a method to investigate GLP1R+ neuron function in emesis.
Conclusions:
- A novel saporin conjugate effectively ablates GLP1R+ cells, offering a valuable research tool.
- This tool enables targeted manipulation of area postrema GLP1R+ neurons in the Suncus murinus.
- Further research can elucidate the role of these neurons in GLP1R agonist-induced emesis.
