Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease.
Previous studies in Creutzfeldt-Jakob disease (CJD) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. Microglia can show an activated phenotype before prion protein (PrP) pathology is detectable in brain, and isolated infectious microglia contain very little PrP. To find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed RNA from isolated microglia with relevant cDNA arrays, and identified approximately 30 transcripts not previously examined in any transmissible spongiform encephalopathy. This CJD expression profile contrasted with that of uninfected microglia exposed to prototypic inflammatory stimuli such as lipopolysaccharide and IFN-gamma, as well as PrP amyloid. These findings underscore inflammatory pathways evoked by the infectious agent in brain. Transcript profiles unique for CJD microglia and other myeloid cells provide opportunities for more sensitive preclinical diagnoses of infectious and noninfectious neurodegenerative diseases.
Baker
Christopher A
CA
Section of Neuropathology, Yale University School of Medicine, 333 Cedar Street, FMB 11, New Haven, CT 06510, USA.
Manuelidis
Laura
L
D000818:Animals; D002478:Cells, Cultured; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018620:PrPSc Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008070:Lipopolysaccharides; D018620:PrPSc Proteins; D007371:Interferon-gamma