Cellular prion protein localization in rodent and primate brain.

The presence of an abnormal, protease-resistant form of the prion protein (PrP) is the hallmark of various forms of transmissible spongiform encephalopathies (TSE) which can affect a number of mammalian species, including humans. The normal, cellular form of this protein, PrPc, while abundant in brain is also present in many tissues and a number of species. In order to address the unresolved question of the precise localization of normal cerebral PrPc, we used a free-floating immunohistochemistry procedure to localize the protein at both the light and the electron microscopic levels in the brain of three TSE-sensitive species: hamster, macaque and humans. This method shows that PrPc is abundant in synaptic terminal fields in olfactory bulb, limbic-associated structures and in the striato-nigral complex, whereas many other regions of the hamster brain are essentially devoid of immunoreactivity. With the striking exception of the olfactory nerve, in which axons are continually growing throughout life, PrPc is not abundant in fibre pathways. PrPc distribution in the primate hippocampus and cortex is very similar to the distribution observed in hamster. PrPc was present at synaptic profiles as shown by immunoelectron microscopy, but was not detectable in neuronal perikaryon either by light or electron microscopy. Our results show that PrPc is abundant in a number of brain structures known for ongoing plasticity, and are consistent with the hypothesis that the protein also plays a role in synaptic function.