Related Experiment Video
Updated: Dec 18, 2025
Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease
Janne M Toivonen1,2,3,4, David Sanz-Rubio1,2, Óscar López-Pérez1,2,3,4,5,6
1Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, University of Zaragoza, 50013 Zaragoza, Spain.
Abstract:
MicroRNAs (miRNAs) may contribute to the development and pathology of many neurodegenerative diseases, including prion diseases. They are also promising biomarker candidates due to their stability in body fluids. We investigated miRNA alterations in a Tg501 mouse model of prion diseases that expresses a transgene encoding the goat prion protein (PRNP). Tg501 mice intracranially inoculated with mouse-adapted goat scrapie were compared with age-matched, mock inoculated controls in preclinical and clinical stages. Small RNA sequencing from the cervical spinal cord indicated that miR-223-3p, miR-151-3p, and miR-144-5p were dysregulated in scrapie-inoculated animals before the onset of symptoms. In clinical-stage animals, 23 significant miRNA alterations were found. These miRNAs were predicted to modify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including prion disease, extracellular matrix interactions, glutaminergic synapse, axon guidance, and transforming growth factor-beta signaling. MicroRNAs miR-146a-5p (up in cervical spinal cord) and miR-342-3p (down in cervical spinal cord, cerebellum and plasma), both indicated in neurodegenerative diseases earlier, were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Minimal changes observed before the disease onset suggests that most miRNA alterations observed here are driven by advanced prion-associated pathology, possibly limiting their use as diagnostic markers. However, the results encourage further mechanistic studies on miRNA-regulated pathways involved in these neurodegenerative conditions.
Insights
MicroRNA (miRNA) changes in prion disease models were identified. While early alterations were minimal, later stages showed significant miRNA dysregulation, suggesting limited diagnostic potential but highlighting pathways for future research.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in neurodegenerative diseases, including prion diseases.
- Their stability in body fluids makes them potential biomarkers.
Purpose of the Study:
- Investigate miRNA alterations in a Tg501 mouse model of prion disease.
- Identify potential miRNA biomarkers and affected pathways.
Main Methods:
- Small RNA sequencing of cervical spinal cord from Tg501 mice and controls at preclinical and clinical stages.
- Quantitative real-time PCR (qRT-PCR) for validation.
Main Results:
- Dysregulation of miR-223-3p, miR-151-3p, and miR-144-5p observed before symptom onset.
- 23 significant miRNA alterations identified in clinical stage, impacting pathways like prion disease and glutamatergic synapse.
- miR-146a-5p and miR-342-3p changes confirmed via qRT-PCR.
Conclusions:
- Most miRNA alterations occur in advanced prion disease pathology, potentially limiting early diagnostic utility.
- Further research into miRNA-regulated pathways is warranted for understanding neurodegeneration mechanisms.
