Ghrelin system regulates neurons of the supramammillary nucleus

JULIETA PAOLA AGUGGIA, MARÍA PAULA CORNEJO, FRANCO BARRILE, MIRTA REYNALDO, GUADALUPE GARCÍA ROMERO, DANIELA CASSANO, PABLO NICOLÁS DE FRANCESCO, GIMENA FERNANDEZ, MAIA URIARTE DONATI, SPRING VALDIVIA, MARÍA JOSÉ TOLOSA, MARIO PERELLO

Villa Carlos Paz

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de Neurociencias

Ghrelin is a stomach-derived hormone that acts via the growth hormonesecretagogue receptor (GHSR) and regulates a variety of physiological functions.GHSR is expressed in the supramammillary nucleus (SuM), a hypothalamic areainvolved in behaviors associated with food intake, food-reward and novelty.However, the effects of ghrelin in the SuM are uncertain. Here we used mice, inwhich the enhanced green fluorescent protein (eGFP) is expressed under thecontrol of the GHSR promoter (GHSR-eGFP mice), to gain neuroanatomical andfunctional insights of the GHSR neurons of the SuM. First, we validated the GHSReGFPmice as a reporter model for GHSR neurons in the SuM. We found thatGHSR-eGFP mice contain a ~ 400,39±20 eGFP+ cells in the SuM, and that~53,19 % of them express GHSR. In GHSR-eGFP mice, we found that GHSRneurons of the SuM do not produce GABA or dopamine. In wild-type mice, wefound that systemic administration of ghrelin, fasting and fasting-induced refeedingdo not induce increase of the marker of neuronal activation c-Fos in the SuM. Incontrast, intra-VTA-injected ghrelin, high-fat diet bingeing eating, and caloricrestriction increase of c-Fos levels in the SuM. Thus, current data suggest thatGHSR signaling activates neurons of the SuM under specific experimentalconditions.