A neurotoxic prion protein fragment enhances proliferation of microglia but not astrocytes in culture.
The scrapie isoform of the prion protein (PrPSc) induces pathological changes in the central nervous system including neurodegeneration and gliosis. A synthetic prion protein (PrP) peptide corresponding to amino acid residues 106-126 has been shown to be toxic to neurons that express PrPC, the cellular isoform of PrP. Here we show that in mixed glial cultures PrP106-126 induces astroglial proliferation that is dependent on cellular PrPc expression. In purified cultures of glial subtypes only microglia proliferated in response to PrP106-126. This effect was independent of PrP expression. Destruction of microglia in mixed glial cultures by L-leucine methyl ester (LLME) treatment abolished enhanced proliferation caused by PrP106-126. This proliferative effect can be restored by co-culturing LLME-treated astrocytes with microglia. Microglia therefore seem to mediate the proliferative effect exerted by PrP106-126 on astrocytes.
Institut für Neuropathologie and Abteilung Biochemie II, Universität Göttingen, Germany.
D R
DR
Brown
B
B
Schmidt
H A
HA
Kretzschmar
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D018620:PrPSc Proteins / Q000494:pharmacology*; D013268:Stimulation, Chemical
D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D010455:Peptides; D018620:PrPSc Proteins