Replication of prions is dependent on the presence of the host protein
PrPc. During the course of disease, PrPc is converted into an abnorma
l isoform, PrPSc, which accumulates in the brain. Attempts to identify
the cell type(s) in which prion replication and PrP conversion occur
have reached conflicting results. Although PrP mRNA is present in high
amounts in neurons throughout the life of the animal, PrPSc initially
accumulates in astrocytes and possibly other glial cells and, later i
n the course of the disease, spreads diffusely in the tissue, often in
white matter. We report here that PrP mRNA is expressed not only in n
eurons but also in astrocytes and oligodendrocytes throughout the brai
n of postnatal hamsters and rats. The level of glial PrP mRNA expressi
on in neonatal animals was comparable to that of neurons and increased
two-fold during postnatal development. A substantial portion of drain
PrP mRNA is therefore contributed by glial cells. Our results provide
an explanation for the accumulation of PrPSc in white matter tissue a
nd in the cytoplasm of glial cells and argue for a direct involvement
of glia in prion propagation.