Pathology of SSLOW , a transmissible and fatal synthetic prion protein disorder, and comparison with naturally occurring classical transmissible spongiform encephalopathies
Author(s) -
Jeffrey M.,
McGovern G.,
Makarava N.,
González L.,
Kim Y.S.,
Rohwer R. G.,
Baskakov I. V.
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12053
Subject(s) - scrapie , biology , pathology , neuropathology , microglia , virology , immunogold labelling , hamster , cellular pathology , amyloid (mycology) , alpha synuclein , mesocricetus , prion protein , microbiology and biotechnology , immunology , disease , antibody , medicine , inflammation , parkinson's disease
Aims Naturally occurring transmissible spongiform encephalopathies ( TSEs ) accumulate disease‐specific forms of prion protein on cell membranes in association with pathognomonic lesions. We wished to determine whether synthetic prion protein disorders recapitulated these and other subcellular TSE ‐specific changes. Methods SSLOW is a TSE initiated with refolded synthetic prion protein. Five terminally sick hamsters previously intracerebrally inoculated with third passage SSLOW were examined using light and immunogold electron microscopy. Results SSLOW ‐affected hamsters showed widespread abnormal prion protein ( PrP SSLOW ) and amyloid plaques. PrP SSLOW accumulated on plasma lemmas of neurites and glia without pathological changes. PrP SSLOW also colocalized with increased coated vesicles and pits, coated spiral membrane invaginations and membrane microfolding. PrP SSLOW was additionally observed in lysosomes of microglial cells but not of neurones or astrocytes. Conclusions PrP SSLOW is propagated by cell membrane conversion of normal PrP and lethal disease may be linked to the progressive growth of amyloid plaques. Cell membrane changes present in SSLOW are indistinguishable from those of naturally occurring TSEs . However, some lesions found in SSLOW are absent in natural animal TSEs and vice versa. SSLOW may not entirely recapitulate neuropathological features previously described for natural disease. End‐stage neuropathology in SSLOW , particularly the nature and distribution of amyloid plaques may be significantly influenced by the early redistribution of seeds within the inoculum and its recirculation following interstitial, perivascular and other drainage pathways. The way in which seeds are distributed and aggregate into plaques in SSLOW has significant overlap with murine APP overexpressing mice challenged with A β.