The neurochemical nature of PrP(c)-containing cells in the rat brain.

The cellular prion protein (PrP(C)) is a membrane-bound glycoprotein abundantly expressed in neurons and glial cells within the CNS. The scrapie prion protein (PrP(Sc)) is a conformationally altered isoform of PrP(C) that is responsible for prion diseases, also termed transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases that affect a wide variety of mammal species, including humans. The presence of the cellular isoform of PrP is necessary for the establishment and further evolution of prion diseases and the physiological conditions where PrP(C) is present seems to modulate the alterations in TSE. In this work, the presence of PrP(C) in GABAergic, glutamatergic, nitrergic, cholinergic, serotoninergic and orexinergic populations of cells within the rat brain is examined. Our observations show that PrP(C) is widely expressed in a subset of neurons that contain markers of inhibitory populations of cells throughout the rat brain. The presence of PrP(C) in other cells types containing important neurotransmitters for the overall brain function is congruent with the imbalances reported for some of them in TSE. Within the cerebral cortex, PrP(C) is scarcely located in a subset of cells expressing the laminin receptor precursor (LRP) to such a low extent that suggests that other LRP-independent mechanisms actively participate during the pathogenic process. Taken together, our data demonstrate that investigation of the chemical partners of PrP(C) within cells gives a rational basis for the interpretation of the histopathological alterations in TSE and might help analyze some pathogenic mechanisms of PrP(Sc).