Related Experiment Video
Updated: Nov 6, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures
Ajai Tripathi1,2, Ishani Pandit1, Aaron Perles1
1Department of Neurosciences, Cleveland Clinic, Cleveland, Ohio, USA.
Objective:
Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Though MS was initially considered to be a white matter demyelinating disease, myelin loss in cortical gray matter has been reported in all disease stages. We previously identified microRNAs (miRNAs) in white matter lesions (WMLs) that are detected in serum from MS patients. However, miRNA expression profiles in gray matter lesions (GMLs) from progressive MS brains are understudied.
Methods:
We used a combination of global miRNAs and gene expression profiling of GMLs and independent validation using real-time quantitative polymerase chain reaction (RT-qPCR), immuno-in situ hybridization, and immunohistochemistry.
Results:
Compared to matched myelinated gray matter (GM) regions, we identified 82 miRNAs in GMLs, of which 10 were significantly upregulated and 17 were significantly downregulated. Among these 82 miRNAs, 13 were also detected in serum and importantly were associated with brain atrophy in MS patients. The predicted target mRNAs of these miRNAs belonged to pathways associated with axonal guidance, TGF-β signaling, and FOXO signaling. Further, using state-of-the-art human protein-protein interactome network analysis, we mapped the four key GM atrophy-associated miRNAs (hsa-miR-149*, hsa-miR-20a, hsa-miR-29c, and hsa-miR-25) to their target mRNAs that were also changed in GMLs.
Interpretation:
Our study identifies miRNAs altered in GMLs in progressive MS brains that correlate with atrophy measures. As these miRNAs were also detected in sera of MS patients, these could act as markers of GML demyelination in MS.
Insights
Researchers identified specific microRNAs (miRNAs) altered in gray matter lesions of multiple sclerosis (MS) brains. These miRNAs, also found in MS patient serum, correlate with brain atrophy and may serve as biomarkers for gray matter demyelination.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by inflammation, demyelination, and neurodegeneration.
- While initially focused on white matter, gray matter lesions (GMLs) and myelin loss are recognized in all MS stages.
- MicroRNA (miRNA) expression in GMLs of progressive MS brains remains understudied.
Purpose of the Study:
- To investigate miRNA expression profiles in GMLs from progressive MS brains.
- To identify specific miRNAs associated with GMLs and their correlation with clinical measures like brain atrophy.
- To explore the potential of serum-detected miRNAs as biomarkers for GML demyelination.
Main Methods:
- Global miRNA and gene expression profiling of GMLs.
- Validation using real-time quantitative polymerase chain reaction (RT-qPCR), in situ hybridization, and immunohistochemistry.
- Human protein-protein interactome network analysis to map key miRNAs and their targets.
Main Results:
- Identified 82 miRNAs in GMLs, with 10 upregulated and 17 downregulated compared to healthy gray matter.
- Thirteen of these miRNAs were detected in serum and associated with brain atrophy in MS patients.
- Key miRNAs linked to atrophy (hsa-miR-149*, hsa-miR-20a, hsa-miR-29c, hsa-miR-25) were mapped to target mRNAs altered in GMLs, implicating pathways in axonal guidance and signaling.
Conclusions:
- Altered miRNA expression in GMLs of progressive MS brains correlates with atrophy.
- Serum-detected miRNAs associated with GMLs could serve as potential biomarkers for MS gray matter demyelination.
- This study provides novel insights into the molecular mechanisms of gray matter pathology in MS.
