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miR-218 Promotes Dopaminergic Differentiation and Controls Neuron Excitability and Neurotransmitter Release through the Regulation of a Synaptic-Related Genes Network.
Pulcrano, Salvatore; De Gregorio, Roberto; De Sanctis, Claudia; Volpicelli, Floriana; Piscitelli, Rosa Maria; Speranza, Luisa; Perrone-Capano, Carla; di Porzio, Umberto; Caiazzo, Massimiliano; Martini, Alessandro; Giacomet, Cecilia; Medina, Diego; Awatramani, Rajeshwar; Viggiano, Davide; Federici, Mauro; Mercuri, Nicola B; Guatteo, Ezia; Bellenchi, Gian Carlo.
Afiliação
  • Pulcrano S; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • De Gregorio R; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • De Sanctis C; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, New York 10021.
  • Volpicelli F; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • Piscitelli RM; Neuropathology Brain Bank at Mount Sinai, New York, New York 10029.
  • Speranza L; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • Perrone-Capano C; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, 80131, Italy.
  • di Porzio U; Fondazione Santa Lucia Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, 00143, Italy.
  • Caiazzo M; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, New York 10461.
  • Martini A; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • Giacomet C; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, 80131, Italy.
  • Medina D; Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples, 80131, Italy.
  • Awatramani R; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, 80131, Italy.
  • Viggiano D; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, 3584 CG, The Netherlands.
  • Federici M; Fondazione Santa Lucia Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, 00143, Italy.
  • Mercuri NB; Fondazione Santa Lucia Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, 00143, Italy.
  • Guatteo E; Telethon Institute of Genetics and Medicine, Pozzuoli, 80078, Italy.
  • Bellenchi GC; Department of Medical and Translational Science, Federico II University, Naples, 80131, Italy.
J Neurosci ; 43(48): 8104-8125, 2023 11 29.
Article em En | MEDLINE | ID: mdl-37816598
In the brain, microRNAs (miRNAs) are believed to play a role in orchestrating synaptic plasticity at a higher level by acting as an additional mechanism of translational regulation, alongside the mRNA/polysome system. Despite extensive research, our understanding of the specific contribution of individual miRNA to the function of dopaminergic neurons (DAn) remains limited. By performing a dopaminergic-specific miRNA screening, we have identified miR-218 as a critical regulator of DAn activity in male and female mice. We have found that miR-218 is specifically expressed in mesencephalic DAn and is able to promote dopaminergic differentiation of embryonic stem cells and functional maturation of transdifferentiated induced DA neurons. Midbrain-specific deletion of both genes encoding for miR-218 (referred to as miR-218-1 and mir218-2) affects the expression of a cluster of synaptic-related mRNAs and alters the intrinsic excitability of DAn, as it increases instantaneous frequencies of evoked action potentials, reduces rheobase current, affects the ionic current underlying the action potential after hyperpolarization phase, and reduces dopamine efflux in response to a single electrical stimulus. Our findings provide a comprehensive understanding of the involvement of miR-218 in the dopaminergic system and highlight its role as a modulator of dopaminergic transmission.SIGNIFICANCE STATEMENT In the past decade, several miRNAs have emerged as potential regulators of synapse activity through the modulation of specific gene expression. Among these, we have identified a dopaminergic-specific miRNA, miR-218, which is able to promote dopaminergic differentiation and regulates the translation of an entire cluster of synapse related mRNAs. Deletion of miR-218 has notable effects on dopamine release and alters the intrinsic excitability of dopaminergic neurons, indicating a direct control of dopaminergic activity by miR-218.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article