Abstract
Prion diseases are infectious and fatal neurodegenerative diseases. The pathogenic agent is an abnormal prion protein aggregate. Microglial activation in the centre nervous system is a characteristic feature of prion disease. In this study, we examined the effect of PrP 106–126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR. PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106–126, with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly. Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106–126, and indicate that microglial cells might play a critical role in prion pathogenesis.
Key words: Prion, PrP106-126, PrP mRNA, Mouse microglia BV-2 Cells
Footnotes
Foundation items: National Natural Science Foundations of China (30871854); National Science and Technology Supporting Program of China (2006BAD06A13).
References
- 1.Aguzzi A., Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nature. 2006;4:765–775. doi: 10.1038/nrmicro1492. [DOI] [PubMed] [Google Scholar]
- 2.Baker C. A., Lu Z. Y., Zaitsev I., et al. Microglial Activation Varies in Different Models of Creutzfeldt-Jakob Disease. J Virol. 1999;73(6):5089–5097. doi: 10.1128/jvi.73.6.5089-5097.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bai Y., Li Q., Yang J., et al. p75NTR activation of NF-κB is involved in PrP106-126-induced apoptosis in mouse neuroblastoma cells. Neuroscience Res. 2008;62:9–14. doi: 10.1016/j.neures.2008.05.004. [DOI] [PubMed] [Google Scholar]
- 4.Barcikowska M., Liberski P. P., Boellaard J. W., et al. Microglia is a component of the prion protein amyloid plaque in the Gerstmann-Sträussler-Scheinker syndrome. Acta Neuropathol. 1993;85:623–627. doi: 10.1007/BF00334672. [DOI] [PubMed] [Google Scholar]
- 5.Biieler H., Aguzzi A., Sailer A., et al. Mice Devoid of PrP Are Resistant to Scrapie. Cell. 1993;73:1339–1347. doi: 10.1016/0092-8674(93)90360-3. [DOI] [PubMed] [Google Scholar]
- 6.Brandenburg L.-O., Koch T., Sievers J., et al. Internalization of PrP106-126 by the formyl-peptidereceptorlike- 1 in glial cells. J Neurochem. 2007;101:718–728. doi: 10.1111/j.1471-4159.2006.04351.x. [DOI] [PubMed] [Google Scholar]
- 7.Brown D. R., Schmidt B., Kretzschmar H.A. Role of microglia and host protein in neurotoxicity of a prion protein fragment. Nature. 1996;380:345–347. doi: 10.1038/380345a0. [DOI] [PubMed] [Google Scholar]
- 8.Brown H. R., Goller N. L., Rudelli R.D., et al. The mRNA encoding the scrapie agent protein is present in a variety of non-neuronal cells. Acta Neuropathol. 1990;80:1–6. doi: 10.1007/BF00294214. [DOI] [PubMed] [Google Scholar]
- 9.Combs C. K., Johnson D. E., Cannady S. B., et al. Identification of Microglial Signal Transduction Pathways Mediating a Neurotoxic Response to Amyloidogenic Fragments of b-Amyloid and Prion Proteins. J Neuroscience. 1999;19:928–939. doi: 10.1523/JNEUROSCI.19-03-00928.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Forloni G., Angeretti N., Chiesa R., et al. Neurotoxicity of a prion protein fragment. Nature. 1993;362:543–546. doi: 10.1038/362543a0. [DOI] [PubMed] [Google Scholar]
- 11.Giese A., Brown D. R., Groschup M. H., et al. Role of Microglia in Neuronal Cell Death in Prion Disease. Brain Pathol. 2006;8(3):449–457. doi: 10.1111/j.1750-3639.1998.tb00167.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Mchattie S. J., Brown D. R., Bird M. M. Uptake of the prion protein fragment PrP106-126 in vitro. J Neurocytol. 2004;28:149–159. doi: 10.1023/A:1007028323666. [DOI] [PubMed] [Google Scholar]
- 13.Moser M., Colello R. J., Pott U., et al. Developmental Expression of the Prion Protein Gene in Glial Cells. Neuron. 1995;14:509–517. doi: 10.1016/0896-6273(95)90307-0. [DOI] [PubMed] [Google Scholar]
- 14.Muhleisen H., Gehrmann J., Meyermann R. Reactive microgIia in Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol. 1995;21(6):505–517. doi: 10.1111/j.1365-2990.1995.tb01097.x. [DOI] [PubMed] [Google Scholar]
- 15.Sileia V., Fabrizia C., Venturini G., et al. Activation of microglial cells by PrP and β-amyloid fragments raises intracellular calcium through L-type voltage sensitive calcium channels. Brain Res. 1999;818:168–170. doi: 10.1016/S0006-8993(98)01272-4. [DOI] [PubMed] [Google Scholar]
- 16.Tagliavini F., Prelli F., Verga L., et al. Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro. Proc Natl Acad Sci USA. 1993;90:9678–9682. doi: 10.1073/pnas.90.20.9678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Prusiner S. B. Prion Diseases and the BSE Crisis. Science. 1997;278:245–251. doi: 10.1126/science.278.5336.245. [DOI] [PubMed] [Google Scholar]
- 18.Prusiner S. B. Prions. Proc. Natl. Acad. Sci USA. 1998;95:13363–13383. doi: 10.1073/pnas.95.23.13363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Prusiner S. B. Neurodegenerative Diseases and Prions. N Engl J Med. 2001;344(20):1516–1526. doi: 10.1056/NEJM200105173442006. [DOI] [PubMed] [Google Scholar]
- 20.Prusiner S. B., Groth D., Serban A., et al. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA. 1993;90:10608–10612. doi: 10.1073/pnas.90.22.10608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Williamsa A., Lucassenc P. J., Ritchiea D., et al. PrP Deposition, Microglial Activation, and Neuronal Apoptosis in Murine Scrapie. Exp Neurol. 1997;144:433–438. doi: 10.1006/exnr.1997.6424. [DOI] [PubMed] [Google Scholar]
