miRNA profile is altered in a modified EAE mouse model of multiple sclerosis featuring cortical lesions
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Updated: Dec 8, 2025
Simultaneous Isolation of Principal Central Nervous System-Resident Cell Types from Adult Autoimmune Encephalomyelitis Mice
Published on: October 6, 2023
Nicola S Orefice1, Owein Guillemot-Legris2, Rosanna Capasso3
1CEA, Fundamental Research Division (DRF), Institute of Biology Francois Jacob, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France.
Abstract:
Cortical lesions represent a hallmark of multiple sclerosis and are proposed as a predictor of disease severity. microRNAs are suggested to be important players in the disease pathogenesis and the experimental autoimmune encephalomyelitis animal model. We implemented a mouse model recapitulating more closely the human pathology as it is characterized by both an autoimmune heterogeneity and the presence of cortical lesions, two parameters missing in experimental autoimmune encephalomyelitis. In our model, mice clustered in two groups displaying high or low clinical scores. Upon cortical cytokine injection, lesions appeared with a specific topography while cortical miRNA profiles were altered. These two features differed according to disease severity. We evidenced changes in miRNA regulators and targets suggesting that miRNA alteration had functional repercussions that could explain the differences in cortical lesions. This model represents a crucial tool for the study of both miRNA involvement and cortical lesion formation in disease pathogenesis.
Insights
This study introduces a novel mouse model for multiple sclerosis, revealing how microRNA (miRNA) alterations correlate with cortical lesion severity and disease progression, offering new insights into pathogenesis.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Disease Modeling
Background:
- Cortical lesions are key in multiple sclerosis (MS) and predict disease severity.
- MicroRNAs (miRNAs) are implicated in MS pathogenesis and animal models.
- Existing models like experimental autoimmune encephalomyelitis (EAE) lack human-relevant autoimmune heterogeneity and cortical lesions.
Purpose of the Study:
- To develop and characterize a novel mouse model that better recapitulates human MS pathology, including autoimmune heterogeneity and cortical lesions.
- To investigate the role of miRNAs in the development and severity of cortical lesions in this new model.
- To explore the functional consequences of altered miRNA profiles on cortical lesion formation.
Main Methods:
- Implementation of a new mouse model exhibiting autoimmune heterogeneity and cortical lesions.
- Induction of cortical lesions via cytokine injection.
- Analysis of cortical miRNA profiles and their correlation with disease severity and lesion characteristics.
- Identification of miRNA regulators and targets to infer functional impact.
Main Results:
- Mice segregated into high and low clinical score groups.
- Cortical cytokine injection induced lesions with specific topography.
- Altered cortical miRNA profiles were observed and varied with disease severity.
- Changes in miRNA regulators and targets suggest functional repercussions on cortical lesions.
Conclusions:
- The developed mouse model closely mimics human MS pathology, featuring autoimmune heterogeneity and cortical lesions.
- Altered miRNA profiles are linked to disease severity and cortical lesion formation.
- This model is a valuable tool for studying miRNA involvement and cortical lesion pathogenesis in MS.
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