MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival

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 t...

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Main Authors: María Asunción Barreda-Manso, Altea Soto, Teresa Muñoz-Galdeano, David Reigada, Manuel Nieto-Díaz, Rodrigo M. Maza
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/22/16509
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author María Asunción Barreda-Manso
Altea Soto
Teresa Muñoz-Galdeano
David Reigada
Manuel Nieto-Díaz
Rodrigo M. Maza
author_facet María Asunción Barreda-Manso
Altea Soto
Teresa Muñoz-Galdeano
David Reigada
Manuel Nieto-Díaz
Rodrigo M. Maza
author_sort María Asunción Barreda-Manso
collection DOAJ
description 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 processes, apoptosis plays a key role. Several regulators have been described to modulate apoptosis, including post-transcriptional regulation by microRNAs. This study aimed to analyze endogenous expression changes of miR-138-5p, as well as its main validated pro-apoptotic target caspase3, during the maturation of neuronal cultures and their response under apoptotic challenge. Our results point out that the observed opposite expression of miR-138-5p and its target caspase3 might modulate apoptosis favoring 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 results in a reduction of neuronal death. 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.
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spelling doaj.art-72c8224f2bc545ecb1374131910649fb2023-11-24T14:48:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221650910.3390/ijms242216509MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal SurvivalMaría Asunción Barreda-Manso0Altea Soto1Teresa Muñoz-Galdeano2David Reigada3Manuel Nieto-Díaz4Rodrigo M. Maza5Research Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainResearch Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainResearch Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainResearch Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainResearch Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainResearch Unit, Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, SpainNeuronal 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 processes, apoptosis plays a key role. Several regulators have been described to modulate apoptosis, including post-transcriptional regulation by microRNAs. This study aimed to analyze endogenous expression changes of miR-138-5p, as well as its main validated pro-apoptotic target caspase3, during the maturation of neuronal cultures and their response under apoptotic challenge. Our results point out that the observed opposite expression of miR-138-5p and its target caspase3 might modulate apoptosis favoring 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 results in a reduction of neuronal death. 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.https://www.mdpi.com/1422-0067/24/22/16509miR-138-5pmaturationneuroprotectionapoptosisneuronal death
spellingShingle María Asunción Barreda-Manso
Altea Soto
Teresa Muñoz-Galdeano
David Reigada
Manuel Nieto-Díaz
Rodrigo M. Maza
MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
International Journal of Molecular Sciences
miR-138-5p
maturation
neuroprotection
apoptosis
neuronal death
title MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
title_full MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
title_fullStr MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
title_full_unstemmed MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
title_short MiR-138-5p Upregulation during Neuronal Maturation Parallels with an Increase in Neuronal Survival
title_sort mir 138 5p upregulation during neuronal maturation parallels with an increase in neuronal survival
topic miR-138-5p
maturation
neuroprotection
apoptosis
neuronal death
url https://www.mdpi.com/1422-0067/24/22/16509
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