Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus

Title: Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus
Authors: Batool, AasiaHill, Thomas D. M.Nguyen, Ngoc T.Mooney, Catherineet al.
Permanent link: http://hdl.handle.net/10197/11760
Date: 17-Jan-2020
Online since: 2020-11-30T15:58:57Z
Abstract: Repetitive or prolonged seizures (status epilepticus) can damage neurons within the hippocampus, trigger gliosis, and generate an enduring state of hyperexcitability. Recent studies have suggested that microvesicles including exosomes are released from brain cells following stimulation and tissue injury, conveying contents between cells including microRNAs (miRNAs). Here, we characterized the effects of experimental status epilepticus on the expression of exosome biosynthesis components and analyzed miRNA content in exosome-enriched fractions. Status epilepticus induced by unilateral intra-amygdala kainic acid in mice resulted in acute subfield-specific, bi-directional changes in hippocampal transcripts associated with exosome biosynthesis including up-regulation of endosomal sorting complexes required for transport (ESCRT)-dependent and -independent pathways. Increased expression of exosome components including Alix were detectable in samples obtained 2 weeks after status epilepticus and changes occurred in both the ipsilateral and contralateral hippocampus. RNA sequencing of exosome-enriched fractions prepared using two different techniques detected a rich diversity of conserved miRNAs and showed that status epilepticus selectively alters miRNA contents. We also characterized editing sites of the exosome-enriched miRNAs and found six exosome-enriched miRNAs that were adenosine-to-inosine (ADAR) edited with the majority of the editing events predicted to occur within miRNA seed regions. However, the prevalence of these editing events was not altered by status epilepticus. These studies demonstrate that status epilepticus alters the exosome pathway and its miRNA content, but not editing patterns. Further functional studies will be needed to determine if these changes have pathophysiological significance for epileptogenesis.
Funding Details: European Commission - European Regional Development Fund
European Commission - Seventh Framework Programme (FP7)
Funding Details: FutureNeuro industry partners
Type of material: Journal Article
Publisher: Frontiers Media
Journal: Frontiers in Neuroscience
Volume: 13
Start page: 1404
Copyright (published version): 2020 the Authors
Keywords: Non-coding RNANeuroinflammationExtracellular vesicleEpileptogenesisSeizureTemporal lobe
DOI: 10.3389/fnins.2019.01404
Language: en
Status of Item: Peer reviewed
ISSN: 1662-4548
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:Computer Science Research Collection

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