Related Experiment Video
Updated: Jun 28, 2026
Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
A miRNA signature of prion induced neurodegeneration
Reuben Saba1, Chelsey D Goodman, Rhiannon L C H Huzarewich
1Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Center for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Canada.
Abstract:
MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion-induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified.
Insights
This study identified 15 microRNAs (miRNAs) with altered expression in scrapie-infected mouse brains, suggesting a specific miRNA signature in prion-induced neurodegeneration and potential roles in disease pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of cellular processes.
- While miRNAs are known to influence neuronal development, their role in neurodegeneration remains largely unexplored.
Purpose of the Study:
- To investigate miRNA expression changes in the brain during prion-induced neurodegeneration (scrapie).
- To identify specific miRNAs and their potential gene targets involved in disease progression.
Main Methods:
- Microarray and RT-PCR profiling of miRNA expression in scrapie-infected mouse brains.
- Computational prediction of miRNA gene targets.
- Integration of miRNA and mRNA profiling with bioinformatic and biochemical validation.
Main Results:
- Fifteen miRNAs were found to be differentially expressed in scrapie-infected mice.
- A subset of miRNAs, including miR-342-3p and miR-146a, were significantly upregulated, while others like miR-338-3p were downregulated.
- Computational analysis predicted numerous gene targets, with significant overlap with genes already known to be dysregulated in mouse scrapie.
- Correlations were identified between miRNA expression and targets in protein degradation, cell death, synapse function, and neurogenesis pathways.
Conclusions:
- A unique subset of differentially expressed miRNAs characterizes prion-induced neurodegeneration.
- These dysregulated miRNAs and their predicted targets likely play a role in the molecular mechanisms underlying scrapie pathogenesis.
- The findings highlight the potential of miRNAs as biomarkers and therapeutic targets in neurodegenerative diseases.
Related Concept Videos
01:37Neural Regulation
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...