Viral depletion of calcitonin receptors in the area postrema: A proof-of-concept study

Abstract

The area postrema (AP), located in the caudal hindbrain, is one of the primary binding sites for the endocrine satiation hormone amylin. Amylin is co-secreted with insulin from pancreatic ß-cells and binds to heterodimeric receptors that consist of a calcitonin core receptor (CTR) paired with receptor-activity modifying protein (RAMP) 1 or 3. In this study, we aim to validate a CTR-floxed (CTRfl/fl) mouse model for the functional and site-specific depletion of amylin/CTR signaling in the AP and the nucleus tractus solitarius (NTS). CTRfl/fl mice were injected in the NTS with adeno-associated virus (AAV) containing a green fluorescent protein tag (GFP) and Cre recombinase to create a locally restricted knockout of CTR in the caudal hindbrain. KO mice showed a lack of c-Fos expression, a marker for neuronal activation, in the AP, NTS and LPBN after amylin injection. The effect of amylin and salmon calcitonin (sCT), an amylin receptor agonist, on food intake was blunted in KO mice, confirming a functional reduction of amylin signaling in the hindbrain.