Immunohistochemical expression of prion protein (PrPC) in the human forebrain during development.

The cellular prion protein (PrPC) is a ubiquitous protein whose expression in the adult brain occurs mainly in synapses. We used monoclonal antibodies to study fetal and perinatal PrPC expression in the human forebrain. Double immunofluorescence and confocal microscopy with GFAP, Iba1, MAP2, doublecortin, synaptophysin, and GAP-43 were used to localize PrPC. PrPC immunoreactivity was observed in axonal tracts and fascicles from the 11th week to the end of gestation. Synapses expressed PrPC at increasing levels throughout synaptogenesis. At midgestation, a few PrPC-labeled neurons were detected in the cortical anlage and numerous ameboid and intermediate microglial cells were PrPC-positive. In contrast, at the end of gestation, microglial PrPC expression decreased to almost nothing, whereas neuronal PrPC expression increased, most notably in ischemic areas. In adults, PrPC immunoreactivity was restricted to the synaptic neuropil of the gray matter. At all ages, choroid plexus, ependymal, and endothelial cells were labeled, whereas astrocytes were only occasionally immunoreactive. In conclusion, the early expression of PrPC in the axonal field may suggest a specific role for this molecule in axonal growth during development. Moreover, PrPC may play a role in early microglial cell development.