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Sisó, S; Puig, B; Varea, R; Vidal, E; Acín, C; Prinz, M; Montrasio, F; Badiola, J; Aguzzi, A; Pumarola, M; Ferrer, I (2002). Abnormal synaptic protein expression and cell death in murine scrapie. Acta Neuropathologica, 103(6):615-626.

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Reduced expression of synaptophysin p38, synaptic-associated protein of molecular weight 25,000 (SNAP-25), syntaxin-1, synapsin-1, and alpha- and beta-synuclein, matching the distribution of spongiform degeneration, was found in the neurological phase of scrapie-infected mice. In addition, synaptophysin and SNAP-25 were accumulated in isolated neurons, mainly in the thalamus, midbrain and pons, and granular deposits of alpha- and beta-synuclein were present in the neuropil of the same areas. No modifications in the steady state levels of Bcl-2, Bax, Fas and Fas ligand were observed following infection. Yet antibodies against the c-Jun N-terminal peptide, which cross-react with products emerging after caspase-mediate proteolysis, recognize coarse granular deposits in the cytoplasm of reactive microglia. In situ end-labeling of nuclear DNA fragmentation showed positive nuclei with extreme chromatin condensation in the thalamus, pons, hippocampus and, in particular, the granular layer of the cerebellum. More importantly, expression of cleaved caspase-3, a major executioner of apoptosis, was seen in a few cells in the same regions, thus indicating that cell death by apoptosis in scrapie-infected mice is associated with caspase-3 activation. The present findings support the concept that synaptic pathology is a major substrate of neurological impairment and that caspase-3 activation may play a pivotal role in apoptosis in experimental scrapie. However, there is no correlation between decreased synaptic protein expression and caspase-3-associated apoptosis, which suggests that in addition to abnormal prion protein deposition, there may be other factors that distinctively influence synaptic vulnerability and cell death in murine scrapie.


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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:11 Feb 2008 12:25
Last Modified:05 Apr 2016 12:20
Publisher DOI:10.1007/s00401-001-0512-6
PubMed ID:12012094

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