002 | Neuroanatomical analysis of the mouse brain areas where the actions of growth hormone secretagogue receptor and Glucagon-like Peptide-1 Receptor converge

Cellular and Molecular Neurobiology

Author: Julieta Aguggia | Email: JULIAGUGGIA@GMAIL.COM

julieta aguggia , Gimena Fernandez , Franco Barrile , Daniela Cassano , Camila Saenz , Abdella Habib , Mario Perelló

1° Grupo de Neurofisiología, Instituto Multidisciplinario de Biología Celular (IMBICE). Universidad Nacional La Plata (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA). La Plata, Argentina
2° College of Medicine, QU Health, Qatar University, Doha, Qatar.

Ghrelin is a stomach-derived hormone that acts in centrally expressed growth hormone secretagogue receptor (GHSR) and increases food intake as well as glycemia. The Glucagon-like peptide-1 (GLP-1) is a gastrointestinal-derived hormone that acts via the GLP-1 receptor (GLP-1R) in order to reduce food intake and glycemia. Interestingly, GHSR and GLP-1R expression has been observed within many similar brain nuclei suggesting they may act on common neuronal sets to mediate its neurobiological effects. Here, we explored the extent of this putative direct GHSR and GLP-1R interaction in the brain. We mapped the distribution of the GHSR in the mouse brain and examined the localization of this receptor using two complementary approaches: 1) binding of a fluorescent-labeled ghrelin (Fr-ghrelin) in wild-type mice, or 2) visualizing the endogenous fluorescence in GHSR-eGFP mice. In both cases, the presence of GLP-1R was visualized by immunohistochemistry using a validated anti-GLP1R antibody. We found that cells containing both GHSR and GLP-1R are mainly located in the lateral parabrachial nucleus. In contrast, simultaneous presence of GHSR and GLP-1R was much less extensive elsewhere in the brain (e.g. hippocampus, hypothalamus). We also found several areas, such as lateral septal nucleus, medial and basolateral amygdaloid nucleus, rich in GLP-1R fibers that seem to contact GHSR+ neurons. Thus, we conclude that GHSR and GLP-1R largely act on distinct but functionally related cells.