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Prion replication elicits cytopathic changes in differentiated neurosphere cultures.
Yoshifumi Iwamaru1, Takato Takenouchi, Morikazu Imamura
1Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Ibaraki, Japan.
Journal of Virology
|June 7, 2013
Summary
This study introduces a new cell culture model for studying prion diseases. Differentiated neurosphere cultures expressing prion protein show cytotoxicity, revealing mechanisms of prion-induced cell death.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Prion-induced cytotoxicity mechanisms are poorly understood.
- Limited cell culture models exist for studying prion disease cytopathic effects.
Purpose of the Study:
- To develop a novel cell culture model for prion research.
- To investigate the role of prion protein (PrP) in prion-induced cytotoxicity.
- To explore the molecular basis of cell death in prion-infected cells.
Main Methods:
- Established differentiated neurosphere cultures from PrP-null and PrP-expressing mice.
- Infected cultures with various prion strains (Chandler, scrapie, BSE, GSS).
- Assessed abnormal PrP formation, infectivity, cytotoxicity (morphology, viability, LDH), and apoptosis markers (caspase-3, TUNEL).
Main Results:
- PrP-expressing cultures (dNP20) supported de novo prion formation and infectivity.
- Infected dNP20 cultures, particularly astrocytes, showed progressive cytotoxicity and apoptosis.
- PrP-null cultures (dNP0) did not exhibit cytotoxicity, indicating PrP's essential role.
- Caspase inhibition offered partial protection against prion-mediated cell death.
Conclusions:
- Differentiated neurosphere cultures serve as a valuable in vitro bioassay for mouse prions.
- Endogenous PrP expression is crucial for prion-induced cytotoxicity.
- The model facilitates studying the molecular mechanisms of prion neurodegeneration and apoptosis.
