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Detection of MicroRNAs in Microglia by Real-time PCR in Normal CNS and During Neuroinflammation
Published on: July 23, 2012
Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease
Christopher A Baker1, Laura Manuelidis
1Section of Neuropathology, Yale University School of Medicine, 333 Cedar Street, FMB 11, New Haven, CT 06510, USA.
Abstract:
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.
Insights
Infectious Creutzfeldt-Jakob disease (CJD) alters inflammatory gene expression in brain microglia. These unique CJD microglia profiles may enable earlier diagnosis of neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Myeloid and microglial cells are infectious in Creutzfeldt-Jakob disease (CJD).
- Microglia can activate before detectable prion protein (PrP) pathology in the brain.
- Infectious microglia contain minimal PrP, suggesting other mechanisms of activation.
Purpose of the Study:
- To investigate inflammatory gene expression changes in CJD-infected microglia.
- To identify novel transcripts affected by CJD infection in the brain.
Main Methods:
- Analysis of RNA from isolated CJD-infected microglia using cDNA arrays.
- Comparison of CJD microglia gene expression profiles with uninfected microglia exposed to inflammatory stimuli (lipopolysaccharide, IFN-gamma) and PrP amyloid.
Main Results:
- Identification of approximately 30 transcripts not previously studied in transmissible spongiform encephalopathies.
- Distinct inflammatory gene expression profile in CJD microglia compared to controls.
- CJD microglia profiles differ from those induced by standard inflammatory agents or PrP amyloid.
Conclusions:
- CJD infection uniquely modulates inflammatory pathways in brain microglia.
- Unique transcript profiles in CJD microglia and myeloid cells offer potential for sensitive preclinical diagnosis.
- These findings highlight the role of inflammation in CJD pathogenesis and diagnosis.
