Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR-125b-1-3p in neurodevelopmental processes

SCHIZOPHRENIA RESEARCH

卷:205

Article

Cattane, Nadia¹  Mora, Cristina¹  Lopizzo, Nicola¹  Borsini, Alessandra²  Maj, Carlo³  Pedrini, Laura⁴  Rossi, Roberta⁴  Riva, Marco Andrea⁵  Pariante, Carmine Maria²  Cattaneo, Annamaria^1,2 

[1] IRCCS Fatebenefratelli San Giovanni di Dio, Biol Psychiat Unit, Via Pitastroni 4, I-25125 Brescia, Italy

[2] Kings Coll London, Dept Psychol Med, Inst Psychiat, Stress Psychiat & Immunol Lab, 125 Coldharbour Lane, London SE5 9NU, England

[3] Univ Hosp, Inst Genom Stat & Bioinformat, Bonn, Germany

[4] IRCCS Fatebenefratelli San Giovanni di Dio, Psychiat Unit, Via Pilastroni 4, Brescia, Italy

[5] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy

关键词: Schizophrenia;    Early life stress;    Childhood trauma;    miRNAs signature;    miR-125b-1-3p;    Neurodevelopment;    Inflammation;    CXCR4 signaling;    G-alpha signaling;    P2Y purigenic receptor signaling pathway;   

DOI  :  10.1016/j.schres.2018.07.030

来源: Elsevier

【 摘 要 】

Epidemiological and clinical studies have provided evidence for a role of both genetic and environmental factors, such as stressful experiences early in life, in the pathogenesis of Schizophrenia (SZ) and microRNAs (miRNAs) have been suggested to play a key role in the interplay between the environment and our genome. In this study, we conducted a miRNOme analysis in different samples (blood of adult subjects exposed to childhood trauma, brain (hippocampus) of rats exposed to prenatal stress and human hippocampal progenitor cells treated with cortisol) and we identified miR-125b-1-3p as a down-regulated miRNA in all the three datasets. Interestingly, a significant down-regulation was observed also in SZ patients exposed to childhood trauma. To investigate the biological systems targeted by miR-125b-1-3p and also involved in the effects of stress, we combined the list of biological pathways modulated by predicted and validated target genes of miR-125b-13p, with the biological systems significantly regulated by cortisol in the in vitro model. We found, as common pathways, the CXCR4 signaling, the G-alpha signaling, and the P2Y Purigenic Receptor Signaling Pathway, which are all involved in neurodevelopmental processes. Our data, obtained from the combining of miRNAs datasets across different tissues and species, identified miR125b-1-3p as a key marker associated with the long-term effects of stress early in life and also with the enhanced vulnerability of developing SZ. The identification of such a miRNA biomarker could allow the early detection of vulnerable subjects for SZ and could provide the basis for the development of preventive therapeutic strategies. (C) 2018 Published by Elsevier B.V.

【 授权许可】

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