Although the PrPc exists in practically all the tissues of the body, the TSEs only appear in the brain. This is why neurones die and spaces or cavities appear which give rise to the typically "spongy" appearance. What route does the prion follow from the mouth to the brain? This is the great mystery. The first obstacle it encounters is the acidity of the gastric juices, then the action of the enzymes that break up the foods we swallow and then it has to pass through the digestive tract wall. The cells containing the PrPc could be the entry gate but … what cells are they? Are the same in different animal species? Nobody knows.
Answering these questions has been the aim of this thesis and, in order to achieve this objective, we carried out a "sweep" along the digestive tract of rats, primates and of Pyrenean cows – the most affected breed in Navarre. We employed a number of techniques enabling the location of PrPc – using antibodies specifically targeting it. These antibodies, amongst other items, were marked with fluorescent molecules so the positive cells could be subsequently visualised with a microscope.
The results showed that PrPc appears in the endocrine cells that are dispersed throughout the digestive tract. Endocrine cells produce hormones, biochemical messengers that are secreted into the blood and control the correct functioning of the body. This suggests that the conversion of PrPc to PrPsc may occur in these cells and arrive at the brain in the blood. But, in the digestive tract there are dozens of different endocrine cells and not all have PrPc. To identify which ones have and which do not, we detected, simultaneously, the PrPc and another substance, characteristic of each cell type and observed if the marking appeared in the same cells or not. By means of this system we were able to confirm that, curiously, the PrPc appeared in the same cells in all three animal species.
Finally, we also detected PrPc in the nervous system of the wall of the digestive tract. In this case, the disorder may be propagated to the brain through the signals between neurones – the synapses - that link both organs.