NR ATPD
AU Sikorska,B.; Liberski,P.P.; Brown,P.W.
TI Dystrophic Neurites In Scrapie-Affected Brains Are Removed By Autophagy; An Ultrastructural Study
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-14
PT Konferenz-Poster
AB Neuroaxonal dystrophy (NAD) is a form of neuronal degeneration encountered in transmissible spongiform encephalopathies (TSEs). Dystrophic neurites (DN) accumulate various subcellular organelles - electron-dense lysosomal bodies, multivesicular bodies, multilamellar bodies and electron-lucent vesicles of diverse size . It is plausible to suggest that NAD contributes to the overall neuronal loss in TSEs but most investigators believe that neurons in TSEs die by apoptosis or type 1 programmed cell death (PCD) . Another form of neuronal degeneration, autophagy or type 2 of PCD may trigger apoptosis; hence, autophagy and apoptosis are interconnected. We report here that autophagic vesicles developed within dystrophic axons. Ultrathin sections of brains of hamsters inoculated with the 263 K or 22C-H strains of scrapie were stained with lead citrate and uranyl acetate, and specimens were examined using a transmission electron microscope. DN were readily found in practically all specimens of scrapie-affected hamster brains. In a few specimens, both in cross-sections and in longitudinal sections neuronal processes were observed filled with typical NAD inclusions but also containing well-formed autophagic vacuoles. These autophagic vacuoles were virtually identical to those found in much larger number in neuronal somata. They were of different size, usually with double membranes and represented all stages of autophagy. Neither autophagic vacuoles nor other pathological alterations were found in sham-inoculated animals. Thus, we provide for the first time an ultrastructural link between NAD and autophagy in TSE. It is thus plausible that neurites already damaged by NAD are switched to autophagy (or PCD type 2) and then die. Whether neurons still need apoptosis to be removed or whether the formation of robust autophagy is sufficient for their demise is a target for additional study.
AD Beata Sikorska, Pawel P. Liberski, Medical University of Lodz, Poland; Paul Brown, Bethesda, Maryland, USA
SP englisch
PO Deutschland