MiRNA profile is altered in a modified EAE mouse model of multiple sclerosis featuring cortical lesions.

Nicola S Orefice,Giulio G Muccioli,Philippe Hantraye,Pauline Bottemanne,Rosanna Capasso,Owein Guillemot-Legris,Mireille Alhouayek,Michele Caraglia,Giuseppe Orefice

doi:10.7554/elife.56916

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.

Highlights

Multiple sclerosis (MS) has been the subject of many pre-clinical and clinical studies in the last 50 years, its pathogenesis is still not completely understood
EAE mouse model with both a heterogeneous immune response and cortical lesions One of the classical mouse models of MS is the EAE model that is typically induced by subcutaneous administration of myelin-derived peptides in complete Freund’s adjuvant (CFA) followed by intraperitoneal administration of pertussis toxin (PTX)
We found less lesions in the low clinical score (LIS) group compared to the high clinical score (HIS) group, and that the latter could not be distinguished from the PTX group

Summary

Introduction

Multiple sclerosis (MS) has been the subject of many pre-clinical and clinical studies in the last 50 years, its pathogenesis is still not completely understood. MS is a complex and heterogeneous disease presenting various degrees of inflammation, gliosis, and neurodegeneration leading to differences in clinical manifestations and severity between patients (Paz Soldan and Rodriguez, 2002). It is established that these cortical lesions (CLs) represent a hallmark of MS (Lucchinetti et al, 2011; Filippi et al, 2010). CLs were suggested to be predictors of long-term severity in MS (Filippi and Rocca, 2019; Filippi et al, 2010; Treaba et al, 2019). The presence of CLs in patients with a clinically isolated syndrome is suggested as a confirmation for MS diagnosis

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