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: Clémence Girardet, Marion S Bonnet, Rajae Jdir, Medhi Sadoud, Sylvie Thirion, Catherine Tardivel, Julien Roux, Bruno Lebrun, Lourdes Mounien, Jérôme Trouslard, André Jean, Michel Dallaporta, Jean-Denis Troadec
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 124 Issue 1 Pg. 179-91 (Nov 2011) ISSN: 1096-0929 [Electronic] United States
• PMID: 21873375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Trichothecenes
• Intramolecular Oxidoreductases
• PTGES protein, human
• Prostaglandin-E Synthases
• Ptges protein, mouse
• deoxynivalenol
• Dinoprostone

Topics

• Animals
• Anorexia (chemically induced, genetics, immunology)
• Body Temperature (drug effects)
• Brain (drug effects, immunology)
• Cytokines (genetics, immunology)
• Dinoprostone (biosynthesis, physiology)
• Food Contamination
• Gene Expression (drug effects)
• Illness Behavior (drug effects)
• Immunohistochemistry
• Intramolecular Oxidoreductases (genetics)
• Male
• Mice
• Mice, Knockout
• Motor Activity (drug effects)
• Prostaglandin-E Synthases
• Real-Time Polymerase Chain Reaction
• Trichothecenes (toxicity)