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Published on: July 30, 2018
Differentially expressed microRNAs in experimental cerebral malaria and their involvement in endocytosis, adherens
Aarón Martin-Alonso1, Amy Cohen2, María Antonieta Quispe-Ricalde3
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, La Laguna, Islas Canarias, Spain. amalonso@ull.edu.es.
Abstract:
Cerebral malaria (CM) is the most severe manifestation of infection with Plasmodium, however its pathogenesis is still not completely understood. microRNA (miRNA) have been an area of focus in infectious disease research, due to their ability to affect normal biological processes, and have been shown to play roles in various viral, bacterial and parasitic infections, including malaria. The expression of miRNA was studied following infection of CBA mice with either Plasmodium berghei ANKA (causing CM), or Plasmodium yoelii (causing severe but non-cerebral malaria (NCM)). Using microarray analysis, miRNA expression was compared in the brains of non-infected (NI), NCM and CM mice. Six miRNA were significantly dysregulated between NCM and CM mice, and four of these, miR-19a-3p, miR-19b-3p, miR-142-3p and miR-223-3p, were further validated by qPCR assays. These miRNA are significantly involved in several pathways relevant to CM, including the TGF-β and endocytosis pathways. Dysregulation of these miRNA during CM specifically compared with NCM suggests that these miRNA, through their regulation of downstream targets, may be vitally involved in the neurological syndrome. Our data implies that, at least in the mouse model, miRNA may play a regulatory role in CM pathogenesis.
Insights
MicroRNAs (miRNAs) are implicated in cerebral malaria (CM) pathogenesis. Specific miRNAs were dysregulated in the brains of mice with CM compared to non-cerebral malaria, suggesting a regulatory role in this severe neurological syndrome.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Cerebral malaria (CM) is a severe Plasmodium infection with poorly understood pathogenesis.
- MicroRNAs (miRNAs) are key regulators of biological processes and implicated in various infections, including malaria.
- Understanding miRNA roles in CM is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate miRNA expression differences in the brains of mice with CM versus non-cerebral malaria (NCM).
- To identify specific miRNAs potentially involved in CM pathogenesis.
- To explore the pathways regulated by these dysregulated miRNAs.
Main Methods:
- Comparative analysis of miRNA expression in CBA mice infected with Plasmodium berghei ANKA (CM) or Plasmodium yoelii (NCM).
- Microarray analysis of miRNA expression in the brains of non-infected (NI), NCM, and CM mice.
- Quantitative PCR (qPCR) validation of selected dysregulated miRNAs.
Main Results:
- Six miRNAs were significantly dysregulated between NCM and CM groups.
- Four miRNAs (miR-19a-3p, miR-19b-3p, miR-142-3p, miR-223-3p) were validated by qPCR.
- These miRNAs are involved in TGF-β and endocytosis pathways, relevant to CM.
Conclusions:
- Dysregulated miRNAs in CM brains suggest a regulatory role in the neurological syndrome.
- Specific miRNAs may be critical in the pathogenesis of cerebral malaria.
- This study highlights the potential of miRNAs as therapeutic targets in CM.
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