Aberrant Alterations of Mitochondrial Factors Drp1 and Opa1 in the Brains of Scrapie Experiment Rodents

Abstract

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.

Exogenous Hydrogen Sulfide Supplement Attenuates Isoproterenol‐Induced Myocardial Hypertrophy in a Sirtuin 3‐Dependent Manner

“…OPA1 is a vital protein to maintain mitochondrial fusion, while DRP1 is important to regulate mitochondrial fission [46]. Immunofluorescence and western blot were used to detect the expression of the above two proteins.…”

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

“…It is noteworthy that overexpression of Drp1 cannot cause the fragmentation of mitochondria, as the activation of Drp1 activity is determined by the transport of Drp1 from cytoplasm to mitochondria caused by various ( Figure 2) posttranslational modifications (Abe et al, 2017;Choi et al, 2017;C. Guo et al, 2013;Haun et al, 2013;Park, Ko, Hwang, & Koh, 2015;Rizza et al, 2018; H. Wang et al, 2011;Yang et al, 2017).…”

“…Guo et al, 2013;Haun et al, 2013;Park, Ko, Hwang, & Koh, 2015;Rizza et al, 2018;H. Wang et al, 2011;Yang et al, 2017).…”

Modulation of Mitochondrial Dynamics in Neurodegenerative Diseases: An Insight Into Prion Diseases

“…Furthermore, there is a significant decrease in Drp1 in scrapie-infected mice in the terminal stages of disease (139A, ME7 and S15), levels of OPA1 showed a tendency to decrease, and abnormalities of Drp1 and OPA1 were primarily localized to neurons. Collectively, these processes lead to the depression of mitochondrial dynamics and subsequent neuronal apoptosis (Yang et al, 2016 ).…”