Seizures result from hypersynchronous, abnormal firing of neuronal populations and are the primary clinical symptom of the
epilepsies. Brain tissue from animal models and patients with acquired forms of
epilepsy commonly features selective neuronal loss,
gliosis, inflammatory markers and microscopic and macroscopic reorganization of networks. The gene expression landscape is a critical driver of these changes, and gene expression is fine tuned by small, non-coding RNAs called
microRNAs (
miRNAs).
miRNAs inhibit the function of
protein-coding transcripts, resulting in changes in multiple aspects of cell structure and function, including axonal and dendritic structure and the repertoire of
neurotransmitter receptors,
ion channels and transporters that establish neurophysiological functions. Dysregulation of the
miRNA system has emerged as a mechanism that underlies epileptogenesis. Given that
miRNAs can act on multiple
mRNA targets, their manipulation offers a novel, multi-targeting approach to correct disturbed gene expression patterns. Targeting of some
miRNAs has also been used to selectively upregulate individual transcripts, offering the possibility of precision
therapy approaches for disorders of haploinsufficiency. In this Review, we discuss how
miRNAs determine and control neuronal and glial functions, how this process is altered in states associated with hyperexcitability, and the prospects for
miRNA targeting for the treatment of
epilepsy.