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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00389/full |
| _version_ | 1831812688018145280 |
|---|---|
| author | Monica Mazzelli Carlo Maj Nicole Mariani Cristina Mora Veronica Begni Carmine M. Pariante Marco A. Riva Annamaria Cattaneo Annamaria Cattaneo Nadia Cattane |
| author_facet | Monica Mazzelli Carlo Maj Nicole Mariani Cristina Mora Veronica Begni Carmine M. Pariante Marco A. Riva Annamaria Cattaneo Annamaria Cattaneo Nadia Cattane |
| author_sort | Monica Mazzelli |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T21:40:50Z |
| format | Article |
| id | doaj.art-5e760f5587644c9c87baf6b13882cf7f |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-22T21:40:50Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-5e760f5587644c9c87baf6b13882cf7f2022-12-21T18:11:37ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-05-011110.3389/fpsyt.2020.00389523845The Long-Term Effects of Early Life Stress on the Modulation of miR-19 LevelsMonica Mazzelli0Carlo Maj1Nicole Mariani2Cristina Mora3Veronica Begni4Carmine M. Pariante5Marco A. Riva6Annamaria Cattaneo7Annamaria Cattaneo8Nadia Cattane9Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyInstitute for Genomic Statistics and Bioinformatics, University Hospital, Bonn, GermanyStress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United KingdomBiological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyStress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United KingdomDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyBiological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyStress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United KingdomBiological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMicroRNAs (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.https://www.frontiersin.org/article/10.3389/fpsyt.2020.00389/fullearly life stressmiR-19brain trajectoriesneurodevelopmentinflammationdepression |
| spellingShingle | Monica Mazzelli Carlo Maj Nicole Mariani Cristina Mora Veronica Begni Carmine M. Pariante Marco A. Riva Annamaria Cattaneo Annamaria Cattaneo Nadia Cattane The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels Frontiers in Psychiatry early life stress miR-19 brain trajectories neurodevelopment inflammation depression |
| 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 | early life stress miR-19 brain trajectories neurodevelopment inflammation depression |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00389/full |
| work_keys_str_mv | AT monicamazzelli thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT carlomaj thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT nicolemariani thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT cristinamora thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT veronicabegni thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT carminempariante thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT marcoariva thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT annamariacattaneo thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT annamariacattaneo thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT nadiacattane thelongtermeffectsofearlylifestressonthemodulationofmir19levels AT monicamazzelli longtermeffectsofearlylifestressonthemodulationofmir19levels AT carlomaj longtermeffectsofearlylifestressonthemodulationofmir19levels AT nicolemariani longtermeffectsofearlylifestressonthemodulationofmir19levels AT cristinamora longtermeffectsofearlylifestressonthemodulationofmir19levels AT veronicabegni longtermeffectsofearlylifestressonthemodulationofmir19levels AT carminempariante longtermeffectsofearlylifestressonthemodulationofmir19levels AT marcoariva longtermeffectsofearlylifestressonthemodulationofmir19levels AT annamariacattaneo longtermeffectsofearlylifestressonthemodulationofmir19levels AT annamariacattaneo longtermeffectsofearlylifestressonthemodulationofmir19levels AT nadiacattane longtermeffectsofearlylifestressonthemodulationofmir19levels |