P14.-Ghrelin system regulates neurons of the supramammillary nucleus

GUADALUPE GARCÍA-ROMERO; JULIETA AGUGGIA; MARIO PERELLO; MARIA PAULA CORNEJO

Villa Carlos Paz, Córdoba, Argentina

Congreso; XXXIV Reunión Anual SAN 2019; 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 area involved in behaviors associated with food intake, food-reward and novelty. However, the effects of ghrelin in the SuM are uncertain. Here we used mice, in which the enhanced green fluorescent protein (eGFP) is expressed under the control of the GHSR promoter (GHSR-eGFP mice), to gain neuroanatomical and functional insights of the GHSR neurons of the SuM. First, we validated the GHSR-eGFP mice as a reporter model for GHSR neurons in the SuM. We found that GHSR-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 that GHSR signaling activates neurons of the SuM under specific experimental conditions.