title: Brainstem metabotropic glutamate receptors reduce food intake and activate dorsal pontine and medullar structures after peripheral bacterial lipopolysaccharide administration.
abstract: During infection-induced inflammation food intake is reduced. Vagal and brainstem pathways are important both in feeding regulation and immune-to-brain communication. Glutamate is released by vagal afferent terminals in the nucleus of the solitary tract and by its neurons projecting to the parabrachial nuclei. We therefore studied the role of brainstem glutamate receptors in spontaneous food intake of healthy animals and during sickness-associated hypophagia after peripheral administration of bacterial lipopolysaccharides or interleukin-1beta. Brainstem group I and II metabotropic, but not ionotropic, glutamate receptor antagonism increased food intake both in saline- and lipopolysaccharide-treated rats. In these animals, expression of the cellular activation marker c-Fos in the lateral parabrachial nuclei and lipopolysaccharide-induced activation of the nucleus of the solitary tract rostral to the area postrema were suppressed. Group I metabotropic glutamate receptors did not colocalize with c-Fos or neurons regulating gastric function in these structures. Group I metabotropic glutamate receptors were, however, found on raphé magnus neurons that were part of the brainstem circuit innervating the stomach and on trigeminal and hypoglossal motor neurons. In conclusion, our findings show that brainstem metabotropic glutamate receptors reduce food intake and activate the lateral parabrachial nuclei as well as the rostral nucleus of the solitary tract after peripheral bacterial lipopolysaccharide administration. They also provide insight into potential group I metabotropic glutamate receptor-dependent brainstem circuits mediating these effects.
authors.affiliation: CNRS, PsychoNeuroImmunologie, Nutrition et Génétique, UMR 5226, Bordeaux, France; Univ. Bordeaux, PsyNuGen, UMR 5226, Bordeaux, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Chaskiel
authors.affiliation: CNRS, PsychoNeuroImmunologie, Nutrition et Génétique, UMR 5226, Bordeaux, France; Univ. Bordeaux, PsyNuGen, UMR 5226, Bordeaux, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Paul
authors.affiliation: Institut für Veterinär-Physiologie und -Biochemie, Justus-Liebig-Universität Giessen, 35392 Giessen, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Gerstberger
authors.affiliation: Institut für Veterinär-Physiologie und -Biochemie, Justus-Liebig-Universität Giessen, 35392 Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hübschle
authors.affiliation: CNRS, PsychoNeuroImmunologie, Nutrition et Génétique, UMR 5226, Bordeaux, France; Univ. Bordeaux, PsyNuGen, UMR 5226, Bordeaux, France. Electronic address: jan-pieter.konsman@u-bordeaux2.fr.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004926:Escherichia coli; D055809:Illness Behavior / Q000187:drug effects / Q000502:physiology*; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013270:Stomach / Q000294:innervation
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D018094:Receptors, Metabotropic Glutamate; D003345:Corticosterone
keywords: Anorexia; Brainstem; Food intake; Glutamate; Lipopolysaccharide; Nucleus of the solitary tract; Parabrachial nuclei; Sickness behavior