MiR-34a regulates cell proliferation, morphology and function of newborn neurons resulting in improved behavioural outcomes

C. Mollinari, M. Racaniello, A. Berry, M. Pieri, M. C. De Stefano, A. Cardinale, C. Zona, F. Cirulli, E. Garaci, D. Merlo

Research output: Contribution to journalArticle

Abstract

miR-34a is involved in the regulation of the fate of different cell types. However, the mechanism by which it controls the differentiation programme of neural cells remains largely unknown. Here, we investigated the role of miR-34a in neurogenesis and maturation of developing neurons and identified Doublecortin as a new miR-34a target. We found that the overexpression of miR-34a in vitro significantly increases precursor proliferation and influences morphology and function of developing neurons. Indeed, miR-34a overexpressing neurons showed a decreased expression of several synaptic proteins and receptor subunits, a decrement of NMDA-evoked current density and, interestingly, a more efficient response to synaptic stimulus. In vivo, miR-34a overexpression showed stage-specific effects. In neural progenitors, miR-34a overexpression promoted cell proliferation, in migratory neuroblasts reduced the migration and in differentiating newborn neurons modulated process outgrowth and complexity. Importantly, we found that rats overexpressing miR-34a in the brain have better learning abilities and reduced emotionality.

Original languageEnglish
Article numbere1622
JournalCell Death and Disease
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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