![]() ![]() Although the potential role of epigenetic deregulation in the pathogenesis of psychiatric disorders is a major focus of the current research ( 15, 16), the contribution of individual miRNAs in brain development and function and, consequently, in the pathophysiology of psychiatric illnesses is still largely unknown.Įpidemiological and experimental findings indicate that early life adversities occurring during the pre, peri and postnatal period can increase the vulnerability of developing psychiatric disorders later in life ( 17– 19). Therefore, miRNAs have been also named as “master regulators”, because one miRNA can regulate hundreds of genes within a specific biological or cellular pathway and more than half of the protein-coding genes are predicted to be regulated by miRNAs ( 6).Īlterations in miRNAs profiles have been implicated in several psychiatric and neurodevelopmental disorders, as Major Depressive Disorder (MDD) ( 7– 9) and Schizophrenia (SZ) ( 10– 13), two complex and severe diseases characterized by dysregulation of behavior, emotion, and cognition ( 14). Indeed, the miRNA binding, primarily to the 3′UTR of mRNAs, leads to mRNA destabilization or translational repression, resulting in reduced protein levels of the miRNA-target genes ( 5). They are critical regulators of gene expression and exert their activity through the modulation of target mRNA stability or translation efficiency. MicroRNAs (miRNAs) represent one of the major small non-coding RNA classes that have been proposed as regulatory molecules in several biological processes, including neurodevelopment and stress response ( 1– 4). Intervention strategies targeting miR-19 may prevent alterations in these pathways, reducing the ELS-related effects. 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. 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). 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. ![]() 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). 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. 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. 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. 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. MicroRNAs (miRNAs), one of the major small non-coding RNA classes, have been proposed as regulatory molecules in neurodevelopment and stress response. 4Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. ![]() 3Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.2Institute for Genomic Statistics and Bioinformatics, University Hospital, Bonn, Germany.1Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.Riva 4 Annamaria Cattaneo 1 Nadia Cattane 1* Monica Mazzelli 1 Carlo Maj 2 Nicole Mariani 3 Cristina Mora 1 Veronica Begni 4 Carmine M. ![]()
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