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Prion protein‐overexpressing cells show altered response to a neurotoxic prion protein peptide
Author(s) -
Brown David R.
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19981101)54:3<331::aid-jnr4>3.0.co;2-k
Subject(s) - microglia , neurotoxicity , peptide , toxicity , biology , microbiology and biotechnology , prion protein , cell culture , chemistry , biochemistry , immunology , inflammation , medicine , pathology , genetics , disease , organic chemistry
A peptide fragment of the prion protein, PrP106–126 is toxic to neuronal cells in culture. This toxicity is dependent on neuronal expression of the prion protein (PrP c ) and also the presence of microglia. The role of expression of the PrP c in neurotoxicity of this peptide was investigated using mice that overexpress the prion protein. Cells derived from two different strains of PrP c ‐overexpressing mice were used (Tg20 and Tg35). PrP106–126 was more toxic to Tg35 cerebellar cells than wild‐type or Tg20 cells. This increased toxicity required the presence of microglia. Analysis of microglia derived from wild‐type and PrP c ‐overexpressing cells showed that Tg35 microglia were more easily activated than wild‐type microglia, were more easily stimulated to proliferate by astrocytes, and had a higher level of PrP c expression. This may explain the increased PrP106–126 toxicity to Tg35 PrP c ‐overexpressing cerebellar cells. These results suggest that the toxicity of PrP106–126 may depend on the level of expression of PrP c by microglia as well as by neurones. J. Neurosci. Res. 54:331–340, 1998. © 1998 Wiley‐Liss, Inc.