title: Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus.
abstract: Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated.
authors.affiliation: Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology [IMBICE-Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Cabral
authors.affiliation: Image Analysis Laboratory [School of Veterinary Sciences, National University of La Plata and CONICET], La Plata, Buenos Aires, Argentina.
authors.forename: Enrique
authors.initials: E
authors.lastname: Portiansky
authors.affiliation: Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F., Mexico.
authors.forename: Edith
authors.initials: E
authors.lastname: Sánchez-Jaramillo
authors.affiliation: Department of Internal Medicine (Divisions of Hypothalamic Research and Endocrinology), Dallas, Texas, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
authors.affiliation: Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology [IMBICE-Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina. Electronic address: marioperello@yahoo.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Perello
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D018756:GABA Antagonists; D055785:Gene Knockdown Techniques; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D054439:Ghrelin; D009478:Neuropeptide Y; D054440:Receptors, Ghrelin; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; C117416:BIBO 3304; D003345:Corticosterone
keywords: Ghrelin; Neuropeptide Y (NPY); Orexigenic; Stress; γ-Aminobutyric acid (GABA)