Prion-related
encephalopathies are characterized by the accumulation of an abnormal
prion protein isoform (PrPSc) 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 micromolar concentrations of this
peptide as well as
peptides homologous to other portions of PrP, a
peptide corresponding to residues 25-35 of
amyloid-beta 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 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)