Resources
Authors & Affiliations
Petra Bencurova, Albert Sanfeliu, Gary Brennan, David Henshall
Abstract
Voltage-gated sodium channels (Navs) play an integral role in brain function and development, enabling the generation and transmission of electrical signals with implications for neuronal excitability, synapse formation, and circuit establishment. Despite the distinct spatiotemporal expression of Navs, the understanding of their regulation in the developing brain is limited. Here we investigated the involvement of microRNAs (miRNAs), short non-coding RNAs, in the post-transcriptional regulation of sodium channel subunit expression. We carried out Argonaute sequencing on mouse hippocampal tissue samples collected on postnatal days (P) 0, 7, 15, and 22 (n =80, 50% females). We extracted functionally active miRNAs and their target mRNAs via immunoprecipitation of Argonaute proteins and sequenced both RNA species. Our analysis shows that subunits of voltage-gated channels typically expressed in developing hippocampus are bound to Argonaute proteins in mice of both sexes throughout the tested age range (Fig.1). The extent of their regulation by miRNAs increases with hippocampal maturation. We further explored the regulation of two alpha subunits encoded by genes Scn1a and Scn3a with the opposing postnatal expression important for hippocampal function and development. Combining target prediction and weighted correlation network analyses, we identified robust candidate miRNAs predicted to regulate Scn3a (n = 16) and Scn1a (n = 12) expression including those regulating both subunits (n = 7). Our findings demonstrate that miRNAs control subunits of voltage-gated sodium channels in postnatal hippocampal development, suggesting the potential for miRNA-based therapies in the treatment of developmental channelopathies, epilepsies, and other neurological conditions.