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Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS.

Abstract：

:MicroRNAs (miRs) are powerful regulators of CNS development and diseases. Plasma and cerebrospinal fluid (CSF) miRs have recently been implicated as potential new sources for biomarker development. Previously we showed that miR-124-3p, an essential miR for neuronal identity, is highly abundant in neuronal exosomes and its expression decreases in spinal cord of ALS model SOD1G93A mice. In the current study, we found a disease associated reduction of miR-124-3p levels specifically in spinal neurons using in situ hybridization. By employing our recently developed exosome reporter mice in combination with sciatic nerve injections, we observed an increased association of miR-124-3p with spinal motor neuron-derived exosomes in SOD1G93A mice, even at the pre-symptomatic stage. Sciatic nerve injection delivered miR-124-3p is also more frequently localized outside of spinal motor neurons in SOD1G93A mice. Subsequent quantitative analysis of miR-124-3p levels in CSF exosomes from ALS patients found a significant correlation between CSF exosomal miR-124-3p levels and disease stage (indicated by the ALSFRS-R score) of (male) ALS patients. These results provide preliminary evidence to support the potential use of CSF exosomal miR-124-3p as a disease stage indicator in ALS.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Yelick J,Men Y,Jin S,Seo S,Espejo-Porras F,Yang Y

doi

10.1016/j.expneurol.2020.113414

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

113414

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(20)30245-4

journal_volume

333

pub_type

杂志文章

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