Abnormal synaptic protein expression and cell death in murine scrapie
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Abnormal synaptic protein expression and cell death in murine scrapie. / Sisó, S; Puig, B; Varea, R; Vidal, E; Acín, C; Prinz, M; Montrasio, F; Badiola, J; Aguzzi, A; Pumarola, M; Ferrer, I; Puig Martorell, Berta.
In: ACTA NEUROPATHOL, Vol. 103, No. 6, 01.06.2002, p. 615-26.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Abnormal synaptic protein expression and cell death in murine scrapie
AU - Sisó, S
AU - Puig, B
AU - Varea, R
AU - Vidal, E
AU - Acín, C
AU - Prinz, M
AU - Montrasio, F
AU - Badiola, J
AU - Aguzzi, A
AU - Pumarola, M
AU - Ferrer, I
AU - Puig Martorell, Berta
PY - 2002/6/1
Y1 - 2002/6/1
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, Surface
KW - Brain
KW - Caspase 3
KW - Caspases
KW - Cell Death
KW - Crystallins
KW - Down-Regulation
KW - Female
KW - Immunohistochemistry
KW - Male
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred C57BL
KW - Mitogen-Activated Protein Kinases
KW - Nerve Degeneration
KW - Nerve Tissue Proteins
KW - Neuroglia
KW - Neurons
KW - PrPC Proteins
KW - Scrapie
KW - Synapses
KW - Synapsins
KW - Synaptophysin
KW - Synaptosomal-Associated Protein 25
KW - Syntaxin 1
KW - Synucleins
KW - beta-Synuclein
KW - p38 Mitogen-Activated Protein Kinases
U2 - 10.1007/s00401-001-0512-6
DO - 10.1007/s00401-001-0512-6
M3 - SCORING: Journal article
C2 - 12012094
VL - 103
SP - 615
EP - 626
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -