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Published on: November 6, 2013
MiRNA expression profiles in the brains of mice infected with scrapie agents 139A, ME7 and S15
Chen Gao1, Jing Wei1, Bao-Yun Zhang1
1State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), Prion Department, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Abstract:
MicroRNA (miRNA) is a class of non-coding endogenous small-molecule single-stranded RNA that regulates complementary mRNA through degradation or translation of the mRNA targets. Usually, miRNAs show remarkable cell and tissues specificity. Recently, alterations in a set of miRNAs in the brains of patients with certain neurodegenerative diseases, including prion diseases, have been reported. In this study, using deep sequencing technology, miRNA expression profiles in the brains of mice infected with scrapie agents 139A, ME7 and S15 at a terminal stage were comparatively analysed. In total, 57, 94 and 135 differentially expressed miRNAs were identified in the pooled brain samples of 139A-, ME7- and S15-infected mice, respectively, compared with the brains of age-matched normal controls. Among them, 22 were commonly increased and 14 were commonly decreased in the brains of all three infected models. In addition, a reduction in the expression of two novel miRNAs was also commonly observed. Quantitative PCR with reverse transcription analysis of six randomly selected commonly increased and decreased miRNAs in the brains of the three infected mouse models, as well as the two novel miRNAs, verified that the expression patterns were comparable to the deep sequencing data. KEGG analysis of the differentially expressed miRNAs revealed the involvement of similar pathways in all three types of infected animals. Comprehensive analysis of these miRNA profiles not only provides useful clues for understanding prion biology but also is beneficial in the search for possible diagnostic marker(s) for prion diseases.
Insights
MicroRNA (miRNA) expression profiles in the brains of mice with prion diseases reveal common alterations. These findings offer insights into prion biology and potential diagnostic markers for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
- Altered miRNA expression is implicated in neurodegenerative diseases, including prion diseases.
- Prion diseases are characterized by misfolded prion proteins and neurodegeneration.
Purpose of the Study:
- To comparatively analyze miRNA expression profiles in the brains of mice infected with different scrapie agents.
- To identify common differentially expressed miRNAs across multiple prion disease models.
- To explore the potential of these miRNAs as diagnostic markers for prion diseases.
Main Methods:
- Deep sequencing technology was employed to profile miRNA expression in infected mouse brains.
- Quantitative PCR with reverse transcription was used to validate selected miRNA expression levels.
- KEGG pathway analysis was performed on differentially expressed miRNAs.
Main Results:
- Significant numbers of differentially expressed miRNAs were identified in each infected model (57-135 miRNAs).
- Commonly increased (22) and decreased (14) miRNAs were found across all three scrapie models.
- Two novel miRNAs showed commonly reduced expression, and similar pathways were implicated across models.
Conclusions:
- Prion diseases induce distinct yet overlapping miRNA expression changes in the brain.
- Commonly altered miRNAs may serve as valuable biomarkers for prion disease diagnosis.
- Further research into these miRNA profiles can enhance understanding of prion disease pathogenesis.
