MicroRNA-34a Regulates the Depression-like Behavior in Mice by Modulating the Expression of Target Genes in the Dorsal Raphè

Luisa Lo Iacono, Donald Ielpo, Alessandra Accoto, Matteo Di Segni, Lucy Babicola, Sebastian Luca D’Addario, Fabio Ferlazzo, Tiziana Pascucci, Rossella Ventura, Diego Andolina

Research output: Contribution to journalArticle

Abstract

Chronic stress exposure is known to increase vulnerability to the expression of psychiatric disorders, such as depression. Clinical and preclinical evidences support the involvement of the microRNA-34 family in stress-related psychiatric conditions and in the regulation of stress responses. However, the mechanism and the multiple targets by which the microRNA-34 family can affect the stress response and stress-related behavioral alteration are not fully known. Here, with the aid of constitutive and conditional genetic strategy, we examined the role of microRNA-34 family in the expression of depression-like phenotype in mice induced by chronic stress exposure, and we identified their “in vivo” targets during the stressful challenge. We found that microRNA-34a, under chronic stress, is significantly up-regulated in the mouse raphe nuclei, where its recruitment is necessary to induce depression-like behavioral alterations and impact the function of the serotonergic system. Moreover, by next-generation RNA-seq of Ago-2-bound mRNAs, we identified genes that are targeted by microRNA-34a in response to chronic stress and that are likely to mediate its effects.

Original languageEnglish
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Keywords

  • Ago2, RISC-Seq
  • Chronic stress
  • Depression-like behavior
  • MicroRNA-34
  • Raphe nuclei
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

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