Correlative light and electron microscopy studies of PrP localisation in 87V scrapie

Visualization of Prion Infection in Transgenic Mice Expressing Green Fluorescent Protein-Tagged Prion Protein

“…Immunohistochemical studies with the light microscope typically describe several different patterns of PrP Sc deposition in the brain, depending on prion strain and host, including dense plaques, diffuse plaques, granular deposits within the neuropil ("synaptic-like"), and perineuronal aggregates (Jeffrey et al, 1992(Jeffrey et al, , 1994bDeArmond et al, 2004). Most of these deposits appear to be extracellular, a conclusion that is confirmed by electron microscopic studies that have identified both fibrillar and nonaggregated forms of PrP Sc in spaces surrounding neurons and their processes (DeArmond et al, 1985;Jeffrey et al, 1994aJeffrey et al, , 1997.…”

“…Unfortunately, these procedures also irreversibly damage cellular structures and can degrade or redistribute PrP Sc . The requirement for antigen retrieval creates particular difficulties in localizing PrP Sc at the subcellular level, and most PrP Sc deposits visualized in brain sections by light or electron microscopic techniques are extracellular (Jeffrey et al, 1992(Jeffrey et al, , 1994bDeArmond et al, 2004). Thus, we know very little about the intracellular compartments in which PrP Sc accumulates and in which the initial events in PrP Sc formation are likely to occur.…”

Uptake and Neuritic Transport of Scrapie Prion Protein Coincident with Infection of Neuronal Cells

“…In the brains of TSE-infected hosts, PrP-res usually accumulates in both plasmalemmal and extracellular deposits but can also be seen occasionally in late endosome/lysosome-like structures in neurons (Laszlo et al, 1992;Arnold et al, 1995;Grigoriev et al, 1999) and microglia (Jeffrey et al, 1994). These results raise the possibility that neuronal cells might similarly internalize exogenously derived PrP-res when infected for the first time.…”

Prions

“…These experimental studies showed unequivocally that amyloid plaques need not accompany prion replication. In earlier studies, the 87V prion strain that produced numerous amyloid plaques was isolated from Cheviot sheep with scrapie and resulted in amyloid when passaged in Prnp b/b mice (Bruce et al 1976;Jeffrey et al 1994). …”