Circulating ghrelin regulates gaba neurons of the area postrema and mediates gastric emptying in male mice

CABRAL A; CORNEJO MP; FERNANDEZ G; DE FRANCESCO PN; GARCÍA-ROMERO G; URIARTE M; ZIGMAN JM; PORTIANSKY E; REYNALDO M; PERELLO M

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2017 vol. 158 p. 1436 - 1449

0013-7227

Ghrelin is known to act on the area postrema (AP), a sensory circumventricular organlocated in the medulla oblongata that regulates a variety of important physiological functions. However, the neuronal targets of ghrelin in the AP and their potential role are currently unknown. Here, we used wild-type and genetically modified mice to get insights into the neurons of the AP expressing the ghrelin receptor (GHSR) and their role. We show that circulating ghrelin mainly accesses the AP but not to the adjacent nucleus of the solitary tract. Also, we show that peripheral administration of ghrelin and fasting induce an increase of c-Fos, a marker of neuronal activation, in GHSR-expressing neurons of the AP, and that GHSR expression is necessary for the fasting-induced activation of AP neurons. In addition, we show that ghrelin sensitive neurons of the AP are mainly GABAergic, and that an intact AP is required for ghrelininduced gastric emptying. Overall, we show that the capacity of circulating ghrelin to acutely induce gastric emptying in mice requires the integrity of the AP, which contains a population of GABA neurons that are a key target of plasma ghrelin.