Aberrant Alterations of Mitochondrial Factors Drp1 and Opa1 in the Brains of Scrapie Experiment Rodents
- 341 Downloads
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed. Significant decreases of brain Drp1 were observed in scrapie-infected rodents at terminal stage by Western blots and immunohistochemical assays, while the levels of Opa1 also showed declined tendency in the brains of scrapie-infected rodents. Immunofluorescent assays illustrated well localization of Drp1 or Opa1 within NeuN-positive cells. Moreover, the S-nitrosylated forms of Drp1significantly increased in the brain tissues of 139A- and ME7-infected mice at terminal stage. Dynamic analysis of Drp1 and SNO-Dpr1 in the brains collected at different time points within the incubation period of 139A-infected mice demonstrated that the whole Drp1 decreased at all tested samples, whereas the SNO-Drp1 remarkably increased in the sample of 90-day post-infection (dpi), reached to the peak in that of 120 dpi and dropped down but still maintained at higher level at the end of disease. The levels of apoptotic factors cleaved caspase 9, caspase 3, and Bax were also markedly increased in the brain tissues of the mice infected with agents 139A and ME7. Our data indicate a disorder of mitochondria dynamics in the brains of prion infection, largely depending on the abnormal alteration of brain Drp1.
KeywordsScrapie Mitochondria dynamics Drp1 Opa1 Apoptosis
This work was supported by Chinese National Natural Science Foundation grants (81301429, 81572048, and 81630062), National Key Research and Development Plan (2016YFC1202700), and SKLID Development grant (2012SKLID102, 2015SKLID503, and 2016SKLID603).
- Chen LN, Shi Q, Zhang BY, Zhang XM, Wang J, et al. (2015b) Proteomic analyses for the global S-nitrosylated proteins in the brain tissues of different human prion diseases. Mol NeurobiolGoogle Scholar
- Chen LN, Sun J, Yang XD, Xiao K, Lv Y, et al. (2016) The brain NO levels and NOS activities ascended in the early and middle stages and descended in the terminal stage in scrapie-infected animal models. Mol Neurobiol.Google Scholar
- Shi Q, Xiao K, Zhang BY, Zhang XM, Chen LN et al (2015a) Successive passaging of the scrapie strains, ME7-ha and 139A-ha, generated by the interspecies transmission of mouse-adapted strains into hamsters markedly shortens the incubation times, but maintains their molecular and pathological properties. Int J Mol Med 35:1138–1146PubMedGoogle Scholar
- Wang H, Tian C, Fan XY, Chen LN, Lv Y et al (2015) Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction. Int J Biochem Cell Biol 62:24–35CrossRefPubMedGoogle Scholar
- Xiao K, Zhang BY, Zhang XM, Wang J, Chen C, et al. (2016) Re-infection of the prion from the scrapie infected cell line SMB-S15 in three strains of mice, CD1, C57BL/6 and Balb/c. Int J Mol MedGoogle Scholar