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Molecular Neurobiology

, Volume 56, Issue 12, pp 8617–8627 | Cite as

The microRNA-29a Modulates Serotonin 5-HT7 Receptor Expression and Its Effects on Hippocampal Neuronal Morphology

  • Floriana VolpicelliEmail author
  • L. Speranza
  • S. Pulcrano
  • R. De Gregorio
  • M. Crispino
  • C. De Sanctis
  • M. Leopoldo
  • E. Lacivita
  • U. di Porzio
  • G. C. Bellenchi
  • C. Perrone-Capano
Article

Abstract

miRNAs are master regulators of gene expression in diverse biological processes, including the modulation of neuronal cytoarchitecture. The identification of their physiological target genes remains one of the outstanding challenges. Recently, it has been demonstrated that the activation of serotonin receptor 7 (5-HT7R) plays a key role in regulating the neuronal structure, synaptogenesis, and synaptic plasticity during embryonic and early postnatal development of the central nervous system (CNS). In order to identify putative miRNAs targeting the 3′UTR of 5-HT7R mouse transcript, we used a computational prediction tool and detected the miR-29 family members as the only candidates. Thus, since miR-29a is more expressed than other members in the brain, we investigated its possible involvement in the regulation of neuronal morphology mediated by 5-HT7R. By luciferase assay, we show that miR-29a can act as a post-transcriptional regulator of 5-HT7R mRNA. Indeed, it downregulates 5-HT7R gene expression in cultured hippocampal neurons, while the expression of other serotonin receptors is not affected. From a functional point of view, miR-29a overexpression in hippocampal primary cultures impairs the 5HT7R-dependent neurite elongation and remodeling through the inhibition of the ERK intracellular signaling pathway. In vivo, the upregulation of miR-29a in the developing hippocampus parallels with the downregulation of 5-HT7R expression, supporting the hypothesis that this miRNA is a physiological modulator of 5-HT7R expression in the CNS.

Keywords

5-HT7R Hippocampus miR-29a Neurite outgrowth Neuronal primary cultures Neuronal structural plasticity 

Notes

Acknowledgments

We are grateful to the Integrated Microscopy Facility of the Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, Naples, IT. We thank Massimiliano Caiazzo who provided the pRev, pVSVG, and pMDL plasmids, and Sara Mancinelli for the Tet-O-FUW-Ires-GFP empty vector.

Funding Information

This work was supported by “Finanziamento Ricerca di Ateneo” from University of Naples Federico II, and by “POR Campania FESR 2014/2020” from Regione Campania (Project N. B61G18000470007).

Compliance with Ethical Standards

Conflict of Interest

GCB is currently seconded at the ERCEA (European Research Council Executive Agency), Bruxelles, Belgium. The views expressed here are purely those of the writer and may not in any circumstances be regarded as stating an official position of the European Commission.

Supplementary material

12035_2019_1690_Fig6_ESM.png (62 kb)
Supplementary Fig. 1

LP-211 treatment does not affect the levels of 5-HT7R protein and miR-29a transcript. P0-P1 mouse hippocampal neuronal cultures were treated at DIV 14 for 2 h with the 5-HT7R agonist LP (100 nM). a The diagram (mean ± SEM, n=3) shows the level of 5-HT7R normalized with that of ß-actin. The image shows a representative Western blot using 5-HT7R and ß-actin antibodies. The protein molecular weight is shown on the left in kilodalton (kDa). b. The diagram shows the relative quantitation of miR-29a (mean ± SEM, n=3) normalized to the reference gene sno202 (2-dCTmethod). (PNG 61.7 kb)

12035_2019_1690_MOESM1_ESM.tif (2.5 mb)
High resolution image (TIF 2.51 mb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Floriana Volpicelli
    • 1
    • 2
    Email author
  • L. Speranza
    • 2
    • 3
  • S. Pulcrano
    • 1
    • 2
    • 4
  • R. De Gregorio
    • 2
    • 5
  • M. Crispino
    • 6
  • C. De Sanctis
    • 2
    • 3
  • M. Leopoldo
    • 7
  • E. Lacivita
    • 7
  • U. di Porzio
    • 2
  • G. C. Bellenchi
    • 2
    • 8
  • C. Perrone-Capano
    • 1
    • 2
  1. 1.Department of PharmacyUniversity of Naples Federico IINaplesItaly
  2. 2.Institute of Genetics and Biophysics “Adriano Buzzati Traverso”CNRNaplesItaly
  3. 3.Department of NeuroscienceAlbert Einstein College of MedicineNew YorkUSA
  4. 4.Department of Neuroscience and Brain TechnologiesIstituto Italiano di TecnologiaGenoaItaly
  5. 5.Department of Molecular PharmacologyAlbert Einstein College of MedicineNew YorkUSA
  6. 6.Department of BiologyUniversity of Naples Federico IINaplesItaly
  7. 7.Department of Pharmacy – Drug ScienceUniversity of Bari Aldo MoroBariItaly
  8. 8.Department of Systems MedicineUniversity of Rome ‘Tor Vergata’RomeItaly

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