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Tytuł pozycji:

The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels

Tytuł :
The Long-Term Effects of Early Life Stress on the Modulation of miR-19 Levels
Autorzy :
Monica Mazzelli
Carlo Maj
Nicole Mariani
Cristina Mora
Veronica Begni
Carmine M. Pariante
Marco A. Riva
Annamaria Cattaneo
Nadia Cattane
Pokaż więcej
Temat :
early life stress
miR-19
brain trajectories
neurodevelopment
inflammation
depression
Psychiatry
RC435-571
Źródło :
Frontiers in Psychiatry, Vol 11 (2020)
Wydawca :
Frontiers Media S.A., 2020.
Rok publikacji :
2020
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
1664-0640
Relacje :
https://www.frontiersin.org/article/10.3389/fpsyt.2020.00389/full; https://doaj.org/toc/1664-0640
DOI :
10.3389/fpsyt.2020.00389
Dostęp URL :
https://doaj.org/article/5e760f5587644c9c87baf6b13882cf7f
Numer akcesji :
edsdoj.5e760f5587644c9c87baf6b13882cf7f
Czasopismo naukowe
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.

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