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.

Mollinari, C., Racaniello, M., Berry, A., Pieri, M., De Stefano, M., Cardinale, A., et al. (2015). MiR-34a regulates cell proliferation, morphology and function of newborn neurons resulting in improved behavioural outcomes. CELL DEATH & DISEASE, 6(1), e1622 [10.1038/cddis.2014.589].

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

PIERI, MASSIMO;ZONA, CRISTINA;GARACI, ENRICO;
2015-01-01

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.
2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09 - FISIOLOGIA
English
Animals; Base Sequence; Bromodeoxyuridine; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Cerebral Cortex; Cognition; Dependovirus; Emotions; Female; MicroRNAs; Microtubule-Associated Proteins; Mitosis; Molecular Sequence Data; Neuritis; Neurons; Neuropeptides; Phenotype; Rats, Wistar; Stem Cells; Behavior, Animal; Cell Shape; Neurogenesis
Mollinari, C., Racaniello, M., Berry, A., Pieri, M., De Stefano, M., Cardinale, A., et al. (2015). MiR-34a regulates cell proliferation, morphology and function of newborn neurons resulting in improved behavioural outcomes. CELL DEATH & DISEASE, 6(1), e1622 [10.1038/cddis.2014.589].
Mollinari, C; Racaniello, M; Berry, A; Pieri, M; De Stefano, M; Cardinale, A; Zona, C; Cirulli, F; Garaci, E; Merlo, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/132190
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