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.