title: The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping.
abstract: Amylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating-inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post-deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose-response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos-expressing neurons in the brainstem was examined by testing for the co-expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter-2 (VGLUT2)-positive boutons, potential glutamatergic input to amylin- and sCT-activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co-expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co-localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos and DBH after amylin or sCT treatment were closely apposed to VGLUT2-positive boutons. Our study suggests that the hindbrain pathways engaged by amylin and sCT share many similarities, including the mediation by AP neurons.
authors.affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, 8057, Switzerland.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Braegger
authors.forename: Lori
authors.initials: L
authors.lastname: Asarian
authors.forename: Kirsten
authors.initials: K
authors.lastname: Dahl
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Lutz
authors.forename: Christina N
authors.initials: CN
authors.lastname: Boyle
mesh_terms: D000818:Animals; D031608:Area Postrema / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002116:Calcitonin / Q000494:pharmacology / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D058228:Islet Amyloid Polypeptide / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014365:Tryptophan Hydroxylase / Q000032:analysis; D050599:Vesicular Glutamate Transport Protein 2 / Q000032:analysis
chemical_list: D058228:Islet Amyloid Polypeptide; D016760:Proto-Oncogene Proteins c-fos; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; C028815:salmon calcitonin; D002116:Calcitonin; D014365:Tryptophan Hydroxylase; D004299:Dopamine beta-Hydroxylase
keywords: AP lesion; VGLUT2; meal pattern analysis; noradrenaline; rat