Ghrelin system regulates neurons of the supramammilary nucleus

AGUGGIA JP; CORNEJO MP; BARRILE F; REYNALDO M; GARCIA ROMERO G; CASSANO D; DE FRANCESCO PN; FERNANDEZ G; URIARTE, MAIA; VALDIVIA S; TOLOSA MJ; PERELLO M

Córdoba

Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue 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 GHSReGFP mice 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 GHSR neurons of the SuM do not produce GABA or dopamine. In wild-type mice, we found that systemic administration of ghrelin, fasting and fasting-induced refeeding do not induce increase of the marker of neuronal activation c-Fos in the SuM. In contrast, intra-VTA-injected ghrelin, high-fat diet bingeing eating, and caloric restriction increase of c-Fos levels in the SuM. Thus, current data suggest thatGHSR signaling activates neurons of the SuM under specific experimental conditions.