Divergent neuronal circuitries underlying orexigenic effects of circulating or cerebrospinal fluid ghrelin: critical role of brain accessibility

AGUSTINA CABRAL; GIMENA FERNANDEZ; ANABELA PATRONE; SPRING VALDIVIA; MIRTA REYNALDO; MARIO PERELLÓ

Congreso; Sociedad Argentina de Neurociencias. XXVIII Annual Meeting.; 2013

Ghrelin is a hormone that stimulate food intake via activation of growth hormonesecretagogue receptor (GHSR). This study was aimed to delineate the neuronalcircuits that mediate the orexigenic effect of ghrelin. First, we analyzed the c-Fosinduction in the brain of mice centrally or systemically treated with ghrelin. Wefound that peripherally administrated ghrelin dose-dependently increased foodintake and number of c-fos positive cells in the hypothalamic arcuate nucleus (ARC)and solitary tract nucleus. In contrast, centrally administrated ghrelin increasedfood intake and number of c-fos positive cells in most nuclei expressing GHSR. Todetermine which nuclei are directly affected by ghrelin, we centrally or systemicallyinjected mice with fluorescein-ghrelin (F-ghrelin). We found that peripherallyinjected F-ghrelin only accessed to the ARC while centrally injected F-ghrelinreached most GHSR-expressing brain areas. Then, we tested ghrelin effects in ARCablatedmice. These mice failed to respond to peripheral ghrelin but fullyresponded to centrally administrated ghrelin. ARC-ablated mice showed similarghrelin-induced c-fos expression as seen in control mice, but in the ARC, where noc-Fos was found. Thus, circulating ghrelin mainly accesses to the ARC, which isrequired for orexigenic effects of the hormone. Cerebrospinal ghrelin accesses to avariety of nuclei, which can mediate the orexigenic effects of the hormone even inthe absence of the ARC.