DONNER - Deoxynivalenol (DON) – Nervous Effects Reconnaissance
Deoxynivalenol (DON), a trichothecene mycotoxin also called vomitoxin due to the characteristic emesis in acute toxicosis, is a secondary metabolite of Fusarium fungi and one of the most prevalent mycotoxins in grain-based food and feed products worldwide. In Europe, humans are generally exposed to DON through the diet chronically at low levels. In Norway, children are exposed to levels close or exceeding the tolerable daily intake (TDI) of 1 μg/kg bw/day. Domestic animals are also sensitive to DON and specific maximal limits for feed- and foodstuffs have been established by the European Union.
Critical effects of non-acute DON intoxication are impairment of the immune system, gastrointestinal and central inflammation, and anorexia (food refusal and loss of weight gain). Furthermore, orally exposed laboratory (mice, rats) and domestic animals (pig, chicken) show dose-dependent behavioural changes such as increased locomotive activity and aggression suggesting that DON might also directly affect the central nervous system (CNS). DON can pass through the blood-brain barrier and modulate brain neuronal activity by influencing the cytokine levels, biogenic monoamines metabolism and secretion of the satiety hormone cholecystokinin. Decreased neural cell viability and increased c-Fos in some brain structures have been shown. Mice have been established as an appropriate model for the study of brain-effective compounds.
Since data on the neurotoxicological effects of DON chronic low-level exposure had been missing so far, the DONNER project has combined expertise of the Norwegian Veterinary Institute (NVI), Oslo, Norway, and the Institute of Cellular and Integrative Neurosciences (INCI), Strasbourg, France, in, respectively, mycotoxinology and neurobiology to address this in vitro in brain cells, and ex vivo/in vivo in mice. The project has established the cooperation between the two institutes by mutual visits and exchange of study materials. The DONNER project is considered as a pilot for further activities in the field of brain mycotoxicosis.
Cellular toxicity was analysed with murine astrocytes and glia cells, brain functions were monitored at the cellular level and different behavioural tests in mice were performed.
First results show that DON decreases the viability and proliferation of nervous cells and leads to the secretion of stress-related cytokines. Chronic low-dose exposure of mice resulted in the excitation of specific brain regions, and significant changes in some behavior experiments. The brain metabolome was monitored, and the distribution of DON in mouse after oral application was determined. DON-glucuronides, the main products of DON biotransformation, were described for the first time in mouse.
Two scientific articles summarising the project results are under writing.
Funding: NFR Aurora/Campus France 2016-2017