Plasma membrane invaginations containing clusters of full-length PrPScare an early form of prion-associated neuropathology in vivo
- Author(s): Godsave, SF
- Wille, H
- Pierson, J
- Prusiner, SB
- Peters, PJ
- et al.
Published Web Locationhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596824/
During prion disease, cellular prion protein (PrPC) is refolded into a pathogenic isoform (PrPSc) that accumulates in the central nervous system and causes neurodegeneration and death. We used immunofluorescence, quantitative cryo-immunogold EM, and tomography to detect nascent, full-length PrPScin the hippocampus of prion-infected mice from early preclinical disease stages onward. Comparison of uninfected and infected brains showed that sites containing full-length PrPSccould be recognized in the neuropil by bright spots and streaks of immunofluorescence on semi-thin (200-nm) sections, and by clusters of cryo-immunogold EM labeling. PrPScwas found mainly on neuronal plasma membranes, most strikingly on membrane invaginations and sites of cell-to-cell contact, and was evident by 65 days postinoculation, or 54% of the incubation period to terminal disease. Both axons and dendrites in the neuropil were affected. We hypothesize that closely apposed plasma membranes provide a favorable environment for prion conversion and intercellular prion transfer. Only a small proportion of clustered PrP immunogold labeling was found at synapses, indicating that synapses are not targeted specifically in prion disease. © 2013 Elsevier Inc.
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