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The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels
MicroRNAs (miRNAs), one of the major small non-coding RNA classes, have been proposed as regulatory molecules in neurodevelopment and stress response. Although alterations in miRNAs profiles have been implicated in several psychiatric and neurodevelopmental disorders, the contribution of individual...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243913/ https://www.ncbi.nlm.nih.gov/pubmed/32499725 http://dx.doi.org/10.3389/fpsyt.2020.00389 |
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author | Mazzelli, Monica Maj, Carlo Mariani, Nicole Mora, Cristina Begni, Veronica Pariante, Carmine M. Riva, Marco A. Cattaneo, Annamaria Cattane, Nadia |
author_facet | Mazzelli, Monica Maj, Carlo Mariani, Nicole Mora, Cristina Begni, Veronica Pariante, Carmine M. Riva, Marco A. Cattaneo, Annamaria Cattane, Nadia |
author_sort | Mazzelli, Monica |
collection | PubMed |
description | MicroRNAs (miRNAs), one of the major small non-coding RNA classes, have been proposed as regulatory molecules in neurodevelopment and stress response. Although alterations in miRNAs profiles have been implicated in several psychiatric and neurodevelopmental disorders, the contribution of individual miRNAs in brain development and function is still unknown. Recent studies have identified miR-19 as a key regulator of brain trajectories, since it drives the differentiation of neural stem cells into mature neurons. However, no findings are available on how vulnerability factors for these disorders, such as early life stress (ELS), can modulate the expression of miR-19 and its target genes. To reach our aim, we investigated miR-19 modulation in human hippocampal progenitor stem cells (HPCs) treated with cortisol during 3 days of proliferation and harvested immediately after the end of the treatment or after 20 days of differentiation into mature neurons. We also analyzed the long-term expression changes of miR-19 and of its validated target genes, involved in neurodevelopment and inflammation, in the hippocampus of adult rats exposed or not to prenatal stress (PNS). Interestingly, we observed a significant downregulation of miR-19 levels both in proliferating (FC = −1.59, p-value = 0.022 for miR-19a; FC = −1.79, p-value = 0.016 for miR-19b) as well as differentiated HPCs (FC = −1.28, p-value = 0.065 for miR-19a; FC = −1.75, p-value = 0.047 for miR-19b) treated with cortisol. Similarly, we found a long-term decrease of miR-19 levels in the hippocampus of adult PNS rats (FC = −1.35, p-value = 0.025 for miR-19a; FC = −1.43, p-value = 0.032 for miR-19b). Among all the validated target genes, we observed a significant increase of NRCAM (FC = 1.20, p-value = 0.027), IL4R (FC = 1.26, p-value = 0.046), and RAPGEF2 (FC = 1.23, p-value = 0.020).We suggest that ELS can cause a long-term downregulation of miR-19 levels, which may be responsible of alterations in neurodevelopmental pathways and in immune/inflammatory processes, leading to an enhanced risk for mental disorders later in life. Intervention strategies targeting miR-19 may prevent alterations in these pathways, reducing the ELS-related effects. |
format | Online Article Text |
id | pubmed-7243913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72439132020-06-03 The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels Mazzelli, Monica Maj, Carlo Mariani, Nicole Mora, Cristina Begni, Veronica Pariante, Carmine M. Riva, Marco A. Cattaneo, Annamaria Cattane, Nadia Front Psychiatry Psychiatry MicroRNAs (miRNAs), one of the major small non-coding RNA classes, have been proposed as regulatory molecules in neurodevelopment and stress response. Although alterations in miRNAs profiles have been implicated in several psychiatric and neurodevelopmental disorders, the contribution of individual miRNAs in brain development and function is still unknown. Recent studies have identified miR-19 as a key regulator of brain trajectories, since it drives the differentiation of neural stem cells into mature neurons. However, no findings are available on how vulnerability factors for these disorders, such as early life stress (ELS), can modulate the expression of miR-19 and its target genes. To reach our aim, we investigated miR-19 modulation in human hippocampal progenitor stem cells (HPCs) treated with cortisol during 3 days of proliferation and harvested immediately after the end of the treatment or after 20 days of differentiation into mature neurons. We also analyzed the long-term expression changes of miR-19 and of its validated target genes, involved in neurodevelopment and inflammation, in the hippocampus of adult rats exposed or not to prenatal stress (PNS). Interestingly, we observed a significant downregulation of miR-19 levels both in proliferating (FC = −1.59, p-value = 0.022 for miR-19a; FC = −1.79, p-value = 0.016 for miR-19b) as well as differentiated HPCs (FC = −1.28, p-value = 0.065 for miR-19a; FC = −1.75, p-value = 0.047 for miR-19b) treated with cortisol. Similarly, we found a long-term decrease of miR-19 levels in the hippocampus of adult PNS rats (FC = −1.35, p-value = 0.025 for miR-19a; FC = −1.43, p-value = 0.032 for miR-19b). Among all the validated target genes, we observed a significant increase of NRCAM (FC = 1.20, p-value = 0.027), IL4R (FC = 1.26, p-value = 0.046), and RAPGEF2 (FC = 1.23, p-value = 0.020).We suggest that ELS can cause a long-term downregulation of miR-19 levels, which may be responsible of alterations in neurodevelopmental pathways and in immune/inflammatory processes, leading to an enhanced risk for mental disorders later in life. Intervention strategies targeting miR-19 may prevent alterations in these pathways, reducing the ELS-related effects. Frontiers Media S.A. 2020-05-15 /pmc/articles/PMC7243913/ /pubmed/32499725 http://dx.doi.org/10.3389/fpsyt.2020.00389 Text en Copyright © 2020 Mazzelli, Maj, Mariani, Mora, Begni, Pariante, Riva, Cattaneo and Cattane http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Mazzelli, Monica Maj, Carlo Mariani, Nicole Mora, Cristina Begni, Veronica Pariante, Carmine M. Riva, Marco A. Cattaneo, Annamaria Cattane, Nadia The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title | The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title_full | The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title_fullStr | The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title_full_unstemmed | The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title_short | The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels |
title_sort | long-term effects of early life stress on the modulation of mir-19 levels |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243913/ https://www.ncbi.nlm.nih.gov/pubmed/32499725 http://dx.doi.org/10.3389/fpsyt.2020.00389 |
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