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Updated: Feb 24, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
DNA methylation in demyelinated multiple sclerosis hippocampus
Anthony M Chomyk1, Christina Volsko1, Ajai Tripathi1
1Department of Neurosciences, Cleveland Clinic, Cleveland, OH, 44195, USA.
Abstract:
Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased. Comparative methylation profiling identify hypo-methylation within upstream sequences of 6 genes and hyper-methylation of 10 genes in demyelinated MS hippocampus. Genes identified in the current study were also validated in an independent microarray dataset generated from MS hippocampus. Independent validation using RT-PCR revealed that DNA methylation inversely correlated with mRNA levels of the candidate genes. Queries across cell-specific databases revealed that a majority of the candidate genes are expressed by astrocytes and neurons in mouse and human CNS. Taken together, our results expands the list of genes previously identified in MS hippocampus and establish DNA methylation as a mechanism of altered gene expression in MS hippocampus.
Insights
DNA methylation changes in the hippocampus are linked to altered gene expression in Multiple Sclerosis (MS). This study identifies specific DNA methylation patterns in demyelinated MS brain tissue, revealing epigenetic mechanisms in MS.
Area of Science:
- Neuroscience
- Epigenetics
- Immunology
Background:
- Multiple Sclerosis (MS) is an immune-mediated CNS demyelinating disease.
- Hippocampal demyelination and memory deficits are common in MS.
- Previous research indicated altered neuronal gene expression in the MS hippocampus.
Purpose of the Study:
- To investigate alterations in DNA methylation within the hippocampus of MS patients.
- To identify specific genes affected by DNA methylation changes in demyelinated MS hippocampus.
- To establish DNA methylation as a mechanism contributing to gene expression changes in MS.
Main Methods:
- Comparative methylation profiling of demyelinated MS hippocampus.
- Analysis of DNA methyltransferase and de-methylation enzyme mRNA levels.
- Validation of candidate genes using independent microarray and RT-PCR data.
- Cell-specific expression analysis of identified genes.
Main Results:
- Increased mRNA levels of DNA methyltransferases and decreased de-methylation enzymes in MS hippocampus.
- Identification of 6 hypo-methylated and 10 hyper-methylated genes in demyelinated MS hippocampus.
- Inverse correlation between DNA methylation and mRNA levels of candidate genes.
- Candidate genes are primarily expressed in astrocytes and neurons.
Conclusions:
- DNA methylation is altered in the demyelinated MS hippocampus.
- Epigenetic modifications, specifically DNA methylation, play a role in altered gene expression in MS.
- This study expands the list of genes implicated in MS hippocampus and highlights DNA methylation as a key mechanism.
