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Expression of disease-related miRNAs in white-matter lesions of progressive multiple sclerosis brains

Ajai Tripathi1, Christina Volsko1, Ushasi Datta1

  • 1Department of Neurosciences Cleveland Clinic Cleveland Ohio.

Annals of Clinical and Translational Neurology
|May 30, 2019
PubMed
Abstract

Insights

MicroRNA (miRNA) levels in multiple sclerosis (MS) brain lesions correlate with white matter MRI abnormalities. These findings reveal specific miRNAs and cell types involved in MS pathogenesis.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Serum microRNA (miRNA) expression in multiple sclerosis (MS) patients correlates with white matter (WM) magnetic resonance imaging (MRI) abnormalities.
  • The expression and cellular origin of target genes for these miRNAs within the MS brain remain uncharacterized.

Purpose of the Study:

  • To analyze and validate the expression of specific miRNAs in white matter lesions (WMLs) of progressive MS brains.
  • To compare these brain-expressed miRNAs with those previously identified in MS patient sera.

Main Methods:

  • Global miRNA expression profiling was conducted on demyelinated WMLs from progressive MS brains (n=5).
  • Significantly altered miRNAs were compared to serum-derived miRNAs from MS patients.
  • Top dysregulated miRNAs common to both datasets were validated using quantitative PCR (qPCR) and in situ hybridization in an independent MS brain cohort.

Main Results:

  • Eleven miRNAs showed pathogenic similarity and 12 showed protective similarity to those previously found in MS sera correlating with WM MRI abnormalities.
  • Expression of 58% of protective miRNAs (7/12) was decreased in MS lesions compared to normal-appearing tissue.
  • Target genes of these miRNAs were altered in MS lesions, with astrocytes and microglia identified as key cellular expressers.

Conclusions:

  • Specific miRNAs correlating with MRI abnormalities were identified within lesioned MS brain tissue.
  • These findings link serum and brain-based miRNA alterations in MS and implicate astrocytes and microglia in disease pathogenesis.

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