In:
European Journal of Neuroscience, Wiley, Vol. 6, No. 9 ( 1994-09), p. 1415-1422
Abstract:
Prion‐related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrP Sc ) and the deposition of PrP amyloid in the brain. This process is accompanied by neuronal loss and astrogliosis. We recently showed that a synthetic peptide corresponding to residues 106–126 of human PrP is amyloidogenic and causes neuronal death by apoptosis in vitro. In the present study we investigated the effects of 1‐ and 14‐day exposures of rat astroglial cultures to mtcromolar concentrations of this peptide as well as peptides homologous to other portions of PrP, a peptide corresponding to residues 25–35 of amyloid‐β protein, and a scrambled sequence of PrP 106–126. No significant changes were observed after 1‐day exposure of cultures to any peptide. Conversely, 14‐day treatment with PrP 106–126 (50 μM) resulted in a 5‐fold increase in glial fibrillary acidic protein (GFAP) expression, as evaluated by Northern and Western blot analyses, and a 1.5‐fold increment in cell number. Light and electron microscopy immunohistochemistry showed an enlargement in size and density of astroglial processes, and an increase in GFAP‐immunoreactive intermediate filaments. These changes were not observed after 14‐day treatment of cultures with the other peptides, including PrP 106–126 scrambled. The increase in GFAP expression of astroglial cultures exposed to PrP 106–126 was quantitatively similar to that found in scrapie‐infected hamster brains. These results suggest that the PrP region corresponding to residues 106–126 is biologically active, and that cerebral accumulation of peptides including this sequence might be responsible for both the neuronal degeneration and the astrogliosis that occur in prion‐related encephalopathies.
Type of Medium:
Online Resource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.1994.6.issue-9
DOI:
10.1111/j.1460-9568.1994.tb01003.x
Language:
English
Publisher:
Wiley
Publication Date:
1994
detail.hit.zdb_id:
2005178-5
detail.hit.zdb_id:
645180-9
SSG:
12
