title: miR-34a regulates cell proliferation, morphology and function of newborn neurons resulting in improved behavioural outcomes.
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.
authors: 1] Institute of Translational Pharmacology, National Research Council, Rome, Italy [2] Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: C
authors: C
authors: Mollinari
authors: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: M
authors: M
authors: Racaniello
authors: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: A
authors: A
authors: Berry
authors: 1] Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy [2] Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors: M
authors: M
authors: Pieri
authors: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: M C
authors: MC
authors: de Stefano
authors: IRCCS San Raffaele Pisana, Rome, Italy.
authors: A
authors: A
authors: Cardinale
authors: Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors: C
authors: C
authors: Zona
authors: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: F
authors: F
authors: Cirulli
authors: IRCCS San Raffaele Pisana, Rome, Italy.
authors: E
authors: E
authors: Garaci
authors: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
authors: D
authors: D
authors: Merlo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003071:Cognition; D000229:Dependovirus / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004644:Emotions; D005260:Female; D035683:MicroRNAs / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D009443:Neuritis / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine
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