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

Nadia Cattane, Cristina Mora, Nicola Lopizzo, Alessandra Borsini, Carlo Maj, Laura Pedrini, Roberta Rossi, Marco Andrea Riva, Carmine Maria Pariante, Annamaria Cattaneo

Research output: Contribution to journalArticle

Abstract

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-1-3p, 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 miR-125b-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.

Original languageEnglish
JournalSchizophrenia Research
Early online dateJul 26 2018
DOIs
Publication statusE-pub ahead of print - Jul 26 2018

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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