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DNA methylation in demyelinated multiple sclerosis hippocampus.

Anthony M Chomyk1, Christina Volsko1, Ajai Tripathi1

  • 1Department of Neurosciences, Cleveland Clinic, Cleveland, OH, 44195, USA.

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|August 20, 2017
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Summary

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.

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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.