MiR-138-5p upregulation during neuronal maturation parallels with an increase in neuronal survival

Abstract

Neuronal maturation is a process that plays a key role in the development and regeneration of the central nervous system. Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal neuronal maturation are less understood. Among the mechanisms influencing such neuronal maturation process, apoptosis plays a key role. Several regulators have been described to modulate apoptosis, including post-transcriptional regulation by microRNAs. This study aimed to assess whether the strikingly induced miR-138-5p during neuronal maturation contributes to avoiding the neuronal death induced by apoptosis. Our results point out that the observed opposite expression of miR-138-5p and its target Caspase3 might modulate apoptosis favouring neuronal survival at distinct maturation stages. The unchanged expression of miR-138-5p in mature neurons contrasts with the significant downregulation in immature neurons upon apoptotic stimulation. Similarly, immunoblot and individual cellular assays confirmed that during maturation, not only the expression but processing of CASP-3 and caspase activity is reduced after apoptotic stimulation which resulted in a reduction of neuronal death. For all this data, we suggest that the upregulation of miR-138-5p during neuronal maturation is crucial in neuronal survival in pathological or traumatic conditions. Further studies would be needed to determine a more detailed role of miR-138-5p in apoptosis during neuronal maturation and the synergistic action of several microRNAs acting cooperatively on Caspase3 or other apoptotic targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/516547v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@e1eb95org.highwire.dtl.DTLVardef@31b0c9org.highwire.dtl.DTLVardef@4d895borg.highwire.dtl.DTLVardef@74c902_HPS_FORMAT_FIGEXP M_FIG C_FIG HighligthsO_LINeuronal maturation promotes cell survival. C_LIO_LINeuronal maturation reduces the processing of CASP-3 and caspase activity after apoptotic stimulation. C_LIO_LIThe expression changes of miR-138-5p and Caspase 3 are opposite during hippocampal neuron maturation. C_LIO_LIThe increase of miR-138-5p expression throughout maturation is not influenced by apoptotic stimulation. C_LIO_LIMiR-138-5p is suggested as an essential factor concerning neuronal maturation, regulating Caspase 3 and favouring survival. C_LI