The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling pathways

L. Speranza, A. Chambery, M. Di Domenico, M. Crispino, V. Severino, F. Volpicelli, M. Leopoldo, G. C. Bellenchi, U. Di Porzio, C. Perrone-Capano

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Serotonergic neurotransmission is mediated by at least 14 subtypes of 5-HT receptors. Among these, the CNS serotonin receptor 7 (5-HTR7) is involved in diverse physiological processes. Here we show that treatment of murine striatal and cortical neuronal cultures with 5-HTR7 agonists (8-OH-DPAT and LP-211) significantly enhances neurite outgrowth. This effect is abolished by the selective 5-HTR7 antagonist SB-269970, by the ERK inhibitor U0126, by the cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine, as well as by cycloheximide, an inhibitor of protein synthesis. These data indicate that 5-HTR7 activation stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK and Cdk5 activation, and de novo protein synthesis. Two-dimensional (2D) gel electrophoresis coupled to Western blot analyses reveals both qualitative and quantitative expression changes in selected cytoskeletal proteins, following treatment of striatal primary cultures with LP-211. In particular, the 34 kDa isoform of MAP1B is selectively expressed in stimulated cultures, consistent with a role of this protein in tubulin polymerization and neurite elongation. In summary, our results show that agonist-dependent activation of the endogenous 5-HTR7 in CNS neuronal primary cultures stimulates ERK- and Cdk5-dependent neurite outgrowth, sustained by modifications of cytoskeletal proteins. These data support the hypothesis that the 5-HTR7 might play a crucial role in shaping neuronal morphology and behaviorally relevant neuronal networks, paving the way to new approaches able to modulate CNS connectivity.

Original languageEnglish (US)
Pages (from-to)155-167
Number of pages13
JournalNeuropharmacology
Volume67
DOIs
StatePublished - Apr 2013
Externally publishedYes

Keywords

  • 5-HTR7
  • Cytoskeletal proteins
  • MAP1B
  • Neurite outgrowth
  • Neuronal primary cultures

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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