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Zawartość zarchiwizowana w dniu 2022-12-23

A study of the neurobiology of parasites of livestock, as a base for developing new anti-parasitic drugs

Cel

Parasite infections constitute a major problem when breeding domestic animals for meat production. The worms inflict often-extensive damage to their hosts by invading different organs and through their nutritional demands. This leads to considerable economic loss. Anti-parasitic drugs are used to control and eradicate the parasites. Unfortunately many parasites have developed resistance to the drugs of today. In the light of growing drug resistance and the paucity of effective helminth vaccines, new types of drugs are urgently needed. When developing anti-parasitic drugs the nervous system (NS) of the worms has often been in focus. In targeting the NS the hope lies in elucidating novel chemotherapeutic agents that act specifically on some neuronal signal substance or its receptor of the worm with minimal side effects on the host.

The aim of this project is to study in detail and from different angles the NS of three model worms from three different groups: Fasciola hepatica (Trematoda) - the liver fluke, Echinococcus multilocularis (Cestoda) - the bladder worm and Ascaris suum (Nematoda) - the pig worm. FMRFamide-related peptides (FaRPs) have been shown to be potently myoactive in all helminth parasites examined. These small peptides occur exclusively in the nervous systems of invertebrates; none has been found in any vertebrate thus far. Their receptors offer immense potential as novel targets in future chemotherapeutic intervention. The FaRPergic system will be better characterised in the three chosen parasites through collaborative studies as outlined in this program. The nitrergic NS that produces nitric oxide (NO), which causes muscle fibres to relax, will also be in focus. Very little is known about the nitrergic NS in parasitic worms. The innervations of the attachment organs and the reproductive organs will be investigated histochemically with NADPH-diaphorase and immunocytochemically with anti-neuronal nitric oxide synthase (nNOS) and anti-cyclic GMP. These data will be compared to the serotoninergic and peptidergic NS.

The spatial relationship between nerves and muscles will be studied with TRITC conjugated phalloidin and HOECHST 333 42 stain for chromatin. Confocal scanning laser microscopy and transmission electron microscopy will be used for the analysis. The character of nNOS in the worms will be analysed radiometrically. Neurophysiological studies will be performed in order to elucidate the function/s of NO in parasitic worms. Different inhibitory and stimulatory agents will be tested. Comparisons of the effects of serotonin and FaRPs with that of NO will be made. The influence of the helminth invasions on the animal host will be followed in detail. The immunological, neurochemical, morphological, biochemical and molecular genetic changes taking place in the hosts will be studied. Furthermore the effects of existing anti-parasitic drugs on the FaRPergic and nitrergic NSs of the worms and their hosts will be studied. These data provide a base for the development of new anti-parasitic drugs.

The project involves two research groups in Russia, one in Armenia, one in Finland and one in the United Kingdom.

The results will be published in international journals and presented at international conferences and workshops.

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Koordynator

Abo Akademi University
Wkład UE
Brak danych
Adres
Artillerigatan 6
20520 Abo
Finlandia

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Uczestnicy (4)