title: Central inflammation and sickness-like behavior induced by the food contaminant deoxynivalenol: a PGE2-independent mechanism.
abstract: Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON consumption constitutes a public health issue. DON stability during processing and cooking explains its large presence in human food. We characterized here DON intoxication by showing that the toxin concomitantly affects feeding behavior, body temperature, and locomotor activity after both per os and central administration. Using c-Fos expression mapping, we identified the neuronal structures activated in response to DON and observed that the pattern of neuronal populations activated by the toxin resembled those induced by inflammatory signals. By real-time PCR, we report the first evidences for a DON-induced central inflammation, attested by the strong upregulation of interleukin-1β, interleukin-6, tumor necrosis factor-α, cyclooxygenase-2, and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However, silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which are resistant to cytokine-induced sickness behavior, did not modify the responses to the toxin. These results reveal that, despite strong similarities, behavioral changes observed after DON intoxication differ from classical sickness behavior evoked by inflammatory cytokines.
authors.affiliation: Département de Physiologie Neurovégétative, Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, Université Paul Cézanne, INRA USC 2027, CNRS UMR 6231, 13397 Marseille, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Girardet
authors.forename: Marion S
authors.initials: MS
authors.lastname: Bonnet
authors.forename: Rajae
authors.initials: R
authors.lastname: Jdir
authors.forename: Medhi
authors.initials: M
authors.lastname: Sadoud
authors.forename: Sylvie
authors.initials: S
authors.lastname: Thirion
authors.forename: Catherine
authors.initials: C
authors.lastname: Tardivel
authors.forename: Julien
authors.initials: J
authors.lastname: Roux
authors.forename: Bruno
authors.initials: B
authors.lastname: Lebrun
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mounien
authors.forename: Jérôme
authors.initials: J
authors.lastname: Trouslard
authors.forename: André
authors.initials: A
authors.lastname: Jean
authors.forename: Michel
authors.initials: M
authors.lastname: Dallaporta
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Troadec
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D005506:Food Contamination; D015870:Gene Expression / Q000187:drug effects; D055809:Illness Behavior / Q000187:drug effects*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D000071876:Prostaglandin-E Synthases; D060888:Real-Time Polymerase Chain Reaction; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D016207:Cytokines; D014255:Trichothecenes; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; C007262:deoxynivalenol; D015232:Dinoprostone