IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Study of circuitries mediating ghrelin-induced activation of hypophysiotropic CRF neurons
Autor/es:
AGUSTINA CABRAL; SPRING VALDIVIA; MIRTA REYNALDO; JESICA RAINGO; MARIO PERELLO
Reunión:
Congreso; Annual meeting of the SfN; 2012
Resumen:
Ghrelin is a stomach-derived hormone that regulates food
intake and neuroendocrine function. Previous evidence indicates that a key
function of ghrelin is to signal stress to the brain via the activation of CRF
(corticotropin-releasing factor)-producing neurons of the hypothalamic
paraventricular nucleus (PVN), which secrete the CRF neuropeptide into the
median eminence and activate the hypothalamic-pituitary-adrenal axis. Recently,
we showed that ghrelin-induced activation of CRF neurons occurs via an indirect
mechanism. Here, we characterized in vivo the neuronal circuit by which
ghrelin activates the hypophysiotropic CRF neurons in mice. We found that
ghrelin administration directly into the PVN (0,1 µg/PVN) activates c-fos --a
marker of cellular activation-- in the CRF neurons of the PVN and the
hypothalamic-pituitary-adrenal axis. It is known that ghrelin receptor is
highly expressed in the neuropeptide Y (NPY)-expressing neurons of the arcuate
nucleus (ARC) and that ghrelin activates these neurons. Thus, we tested whether
this hypothalamic nuclei is required for ghrelin-induced activation of
hypophysiotropic CRF neurons by using mice with the ARC chemically-lesioned by
neonatal treatment with monosodium glutamate (MSG). We found that
intra-cerebro-ventricular (ICV) administration of ghrelin (2 µg/mice) to MSG-treated
mice also activates c-fos in the CRF-producing neurons and the
hypothalamic-pituitary-adrenal axis. MSG mice showed a significant reduction of
NPY neurons in the ARC and NPY-containing fibers in the PVN. To test whether
NPY participates of the ghrelin-induced activation of hypophysiotropic CRF
neurons, we used mice with pharmacological blockage of NPY signaling. For this,
we used the ICV administration of a combination of NPY-1 and NPY-5 selective
receptor antagonists (BIBO3304 and CGP71683 1 µg/mice, respectively) prior to
the administration of ghrelin (2 µg/mice, ICV). We found that mice with
pharmacological blockage of NPY signaling fully responded to ghrelin-induced
activation of hypophysiotropic CRF neurons and hypothalamic-pituitary-adrenal axis.
Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons through a
local neuro-circuitry that is independent of NPY signaling.