Immunolocalization of the cellular prion protein in normal brain

We examined the localization of PrP(c) in normal brain using free-floating section immunohistochemistry and monclonal antibody 3F4. In the mature hamster and baboon brain, PrP(c) is localized to the neuropil with a synaptic distribution and the PrP(c) immunoreactivity is denser in regions known for ongoing plasticity. Cell bodies and major fiber tracts have little or no PrP(c) immunoreactivity. At the electron microscopic level, PrP(c) immunoreactivity decorates synaptic profiles, both pre- and postsynaptically. Results obtained with two additional antibodies, 3B5 and Pri-304, showed similar patterns of PrP(c) bands on Western blots, although Pri-304 was less sensitive. On sections through the adult hamster hippocampus, 3B5 and Pri-304 both stained the synaptic neuropil while cell bodies in the pyramidal and dentate granule cell layers were not immunoreactive. Pri-304 differentiated between synaptic layers in the hippocampus and closely resembled the pattern of staining obtained with 3F4. Preliminary results of developing brain showed that PrP(c) is initially localized along fiber tracts in the neonate brain. These results show that PrP(c) has a synaptic distribution in the adult brain and suggest that there are important changes in its distribution during brain development. These results also characterize two additional reagents for studies of PrP(c) localization.