Study unveils mechanisms behind neurological effects of penitrem A

The mould fungus Penicillium crustosum occurs relatively frequently in food and animal fodder stored in temperate conditions. This mould produces powerful neurotoxins, for example penitrem A, which causes symptoms that are difficult to distinguish from those of other neurological diseases. Angel Moldes-Anaya's doctoral research has shown that penitrem A is capable of penetrating the blood-brain barrier and has unveiled the mechanisms behind the neurological effects of the toxin.

Earlier studies have shown that Penicillium mould often occurs in food and fodder stored in temperate conditions. In Norway, there have been examples of waste food considerably contaminated with Penicillium crustosum. This mould produces penitrems which can have serious toxic effects on the nervous system.

Little is known about how these substances affect the body, especially the brain. Even though there are documented cases of penitrem-induced neurological diseases in both humans and animals, diseases of this kind are probably underdiagnosed. This is because the observable symptoms can be mistaken for those of other neurological diseases, methods of analysis are poor and toxicological and pharmacological expertise is unavailable.

During recent years, more than 10 cases of dogs with attacks resembling epilepsy and impaired motor function have been reported at The Norwegian Veterinary Institute. The common denominator was that all the dogs had eaten food or food waste contaminated with the mould fungus Penicillium crustosum. Angel Moldes used chemical and mycological samples from these dogs in his doctoral project, which has studied the effect of penitrem A on the brain and what happens to the toxin in the body.

Angel Moldes has revealed that penitrem A can penetrate the protective blood-brain barrier and therefore reach the brain itself. Furthermore, he has shown that penitrem A is converted in the liver into more water-soluble metabolites which are easier to excrete from the body. These metabolites do not reach the brain and it is therefore probable that penitrem A is solely responsible for the toxic effect.

Moldes has also studied the mechanism underlying the neurological symptoms observed in both dogs and laboratory animals exposed to the toxin. He found that penitrem A has a substantial effect on GABAA receptors in the brain. GABAA receptors are the major therapeutic target of tranquilisers (diazepam) and anesthetics (barbiturates). Penitrem A may have a tranquilising effect on one part of the brain and a cramp-inducing effect on other parts. Moldes has revealed that oxidative stress can be related to the pathological changes found in animals exposed to penitrems, since these toxins increase the production of free radicals that can damage tissue.

Moldes has moreover isolated and determined the structure of a new substance similar to a penitrem which he detected in a biopsy from one of the affected dogs.



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