In:
Annals of Clinical and Translational Neurology, Wiley, Vol. 6, No. 5 ( 2019-05), p. 854-862
Abstract:
Micro RNA (mi RNA ) expression in the serum of multiple sclerosis ( MS ) patients has been correlated with white matter ( WM ) magnetic resonance imaging ( MRI ) abnormalities. The expression levels and cellular specificity of the target genes of these mi RNA s are unknown in MS brain. Objective The aim of this study was to analyze and validate the expression of mi RNA s, previously reported as dysregulated in sera of MS patients, in white‐matter lesions ( WML s) of progressive MS brains. Methods We performed global mi RNA expression profiling analysis in demyelinated WML s of progressive MS brains ( n = 5) and compared the significantly altered mi RNA s to previously identified mi RNA s from sera of MS patients. Top dysregulated mi RNA s common between the two datasets were validated in an independent cohort of MS brains by quantitative PCR ( qPCR ) and in situ hybridization. Results Among the mi RNA s that were significantly changed in WML tissues, 11 were similar to pathogenic and 12 were common to protective mi RNA s previously identified in sera and correlating with WM MRI abnormalities. Importantly, the expression levels of 58% of the protective mi RNA s (7 of 12) were decreased in MS lesions compared to surrounding normal‐appearing tissue. Target genes of these mi RNA s were also altered in MS lesions and queries of cell‐specific databases identified astrocytes and microglia as the key cellular expressers of these genes in MS brains. Conclusions We identified mi RNA s that correlate with MRI abnormalities in lesioned tissue from MS brains.
Type of Medium:
Online Resource
ISSN:
2328-9503
,
2328-9503
DOI:
10.1002/acn3.2019.6.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2740696-9
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