title: c-Fos immunoreactivity in the pig brain following deoxynivalenol intoxication: focus on NUCB2/nesfatin-1 expressing neurons.
abstract: Deoxynivalenol (DON), produced by the cereal-contaminating Fusarium fungi, is a major trichothecene responsible for mycotoxicoses in farm animals, including swine. The main effect of DON-intoxication is food intake reduction and the consequent body weight loss. The present study aimed to identify brain structures activated during DON intoxication in pigs. To this goal, we used c-Fos staining which constitutes a useful approach to identify activated neurons. We showed that per os administration of Fusarium graminearum extracts (containing the equivalent of 1mg DON per kg of body weight) induced an increase in c-Fos immunoreactivity in several central structures, including the ventrolateral medulla (VLM), dorsal vagal complex (DVC), paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus (Arc), supraoptic nucleus (SON) and amygdala (CeA). Moreover, we coupled c-Fos staining with phenotypic markers detection in order to specify the neuronal populations activated during DON intoxication. This phenotypic characterization revealed the activation of catecholaminergic but not of serotoninergic neurons in response to the toxin. In this context, we also paid a particular attention to NUCB2/nesfatin-1 positive cells, since nesfatin-1 is known to exert a satiety effect. We report here, for the first time in the pig brain, the presence of NUCB2/nesfatin-1 neurons in the VLM, DVC, PVN, Arc and SON, and their activation during DON intoxication. Taken together, these data show that DON stimulates the main structures involved in food intake in pigs and suggest that catecholaminergic and NUCB2/nesfatin-1 neurons could contribute in the anorexigenic effects of the mycotoxin.
authors.affiliation: EA 4674, Laboratoire de Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif, FST St. Jérôme, Aix-Marseille Université, 13013 Marseille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gaigé
authors.forename: Marion S
authors.initials: MS
authors.lastname: Bonnet
authors.forename: Catherine
authors.initials: C
authors.lastname: Tardivel
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinton
authors.forename: Jérôme
authors.initials: J
authors.lastname: Trouslard
authors.forename: André
authors.initials: A
authors.lastname: Jean
authors.forename: Laurence
authors.initials: L
authors.lastname: Guzylack
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Troadec
authors.forename: Michel
authors.initials: M
authors.lastname: Dallaporta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013552:Swine; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002395:Catecholamines; D004268:DNA-Binding Proteins; D009183:Mycotoxins; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos; D014255:Trichothecenes; D012701:Serotonin; C007262:deoxynivalenol