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Gorinski, Nataliya; Bijata, Monika; Prasad, Sonal; Wirth, Alexander; Abdel Galil, Dalia; Zeug, Andre; Bazovkina, Daria; Kondaurova, Elena; Kulikova, Elizabeth; Ilchibaeva, Tatiana; Zareba-Koziol, Monika; Papaleo, Francesco; Scheggia, Diego; Kochlamazashvili, Gaga; Dityatev, Alexander; Smyth, Ian; Krzystyniak, Adam; Wlodarczyk, Jakub; Richter, Diethelm W.; Strekalova, Tatyana; Sigrist, Stephan; Bang, Claudia; Hobuß, Lisa; Fiedler, Jan; [...]

Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors

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  • Medientyp: E-Artikel
  • Titel: Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
  • Beteiligte: Gorinski, Nataliya; Bijata, Monika; Prasad, Sonal; Wirth, Alexander; Abdel Galil, Dalia; Zeug, Andre; Bazovkina, Daria; Kondaurova, Elena; Kulikova, Elizabeth; Ilchibaeva, Tatiana; Zareba-Koziol, Monika; Papaleo, Francesco; Scheggia, Diego; Kochlamazashvili, Gaga; Dityatev, Alexander; Smyth, Ian; Krzystyniak, Adam; Wlodarczyk, Jakub; Richter, Diethelm W.; Strekalova, Tatyana; Sigrist, Stephan; Bang, Claudia; Hobuß, Lisa; Fiedler, Jan; [...]
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-11876-5
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of <jats:italic>Zdhhc21</jats:italic> expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.</jats:p>
  • Zugangsstatus: Freier Zugang