The cellular
prion protein (PrP(C)) is a membrane-bound
glycoprotein mainly present in the CNS. The
scrapie prion protein (PrP(Sc)) is an
isoform of PrP(C), and it is responsible for
transmissible spongiform encephalopathies (TSEs), a group of
neurodegenerative diseases affecting both humans and animals. The presence of the cellular form is necessary for the establishment and further evolution of
prion diseases. Here, we map the regional distribution of PrP(C) in the rat brain and study the chemical nature of these immunopositive neurons. Our observations are congruent with retrograde transport of
prions, as shown by the ubiquitous distribution of PrP(C) throughout the rat brain, but especially in the damaged areas that send projections to primarily affected nuclei in
fatal familial insomnia. On the other hand, the presence of the cellular
isoform in a subset of GABAergic neurons containing
calcium-binding proteins suggests that PrP(C) plays a role in the metabolism of
calcium. The lack of immunostaining in neurons ensheathed by perineuronal nets indicates that
prions do not directly interact with components of these nets. The destruction of these nets is more likely to be the consequence of
a factor needed for
prions during the early stages of TSEs. This would cause destruction of these nets and death of the surrounded neurons. Our results support the view that destruction of this extracellular matrix is caused by the pathogenic effect of
prions and not a primary event in TSEs.