miR-191-5p is a positive regulator of neuronal complexity in the mammalian brain cortex

GONZALEZ, PAULA; SÁNCHEZ IAZURLO, R; AGUIRRE, PAULA A.; DI MARCO, B; ALFONSO, J.; FEDEDA, JUAN PABLO

San Luis

Congreso; XXXVIII Annual Meeting of the SAN; 2023

Sociedad Argentina de Neurociencias

Emerging evidence suggests that microRNAs, critical post-transcriptional regulators ofmRNA translation and stability, plays a crucial role in dendritic and synapticdevelopment.Here, we investigated the role of miR-191, a microRNA implicated in neurodegenerativediseases that is expressed in the murine brain cortex starting from peak corticalneurogenesis.To elucidate the role of miR-191-5p function, we generated a novel approach using theCRISPR/Cas9 system delivered via intra-ventricular injections of the pan-neuronalPHP.eB adeno-associated virus (AAV), to deplete miR-191-5p in the early postnatal micebrain by editing the dicer processing bulge site.Using Golgi-Cox staining coupled with confocal microscopy to assess the morphology ofcortical interneurons by Sholl analysis, we found that depletion of miR-191-5psignificantly shortened the average length of neuronal processes and reduced the totalsurface area of the dendritic tree. Additionally, cortical neurons exhibited decreasedoverall complexity under miR-191-5p depletion, which is consistent with a role for miR191-5p in dendritic development. Tracing the processes of in vitro miR-191-5p depletedvs control N2A cells showed similar results.Overall, this data suggests that miR-191-5p act as a positive regulator of neuronalbranching during brain development. Further experimentation could unravel theregulatory mechanisms governing the observed phenotypes in vivo.