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.

The DONNER project investigates neurotoxicological effects of chronic low-level exposure to DON. The project is a cooperation of the Norwegian Veterinary Institute (NVI), Oslo, Norway, and the Institute of Cellular and Integrative Neurosciences (INCI), Strasbourg, France, combining expertise in mycotoxinology and neurobiology. The effects of low DON concentrations are studied in vitro with murine astrocytes and glia cells, and in vivo in DON-exposed mice by performing different behavioural test.

In a follow-up study, brain mycotoxicosis of DON is currently studied with epigenetics and imaging techniques in different brain regions of chronically exposed mice.

Publications

Fæste CK, Pierre F, Sayyari A, Ivanova L, Massotte D (2018). Chronic low-dose exposure to deoxynivalenol causes behavioural changes in mice.  Arch Toxicol (under writing).

Fæste CK, Solhaug A, Uhlig S, Ivanova L, Pierre F, Massotte D (2018). Deoxynivalenol induces changes in neural cell physiology and the metabolome of exposed mice (under writing).

Funding: NFR Aurora/Campus France 2016-2018.