Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors.
In: Nature communications, Jg. 10 (2019-09-02), Heft 1, S. 3924
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Zugriff:
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 Zdhhc21 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.
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Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors.
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Autor/in / Beteiligte Person: | Gorinski, N ; Bijata, M ; Prasad, S ; Wirth, A ; Abdel Galil, D ; Zeug, A ; Bazovkina, D ; Kondaurova, E ; Kulikova, E ; Ilchibaeva, T ; Zareba-Koziol, M ; Papaleo, F ; Scheggia, D ; Kochlamazashvili, G ; Dityatev, A ; Smyth, I ; Krzystyniak, A ; Wlodarczyk, J ; Richter, DW ; Strekalova, T ; Sigrist, S ; Bang, C ; Hobuß, L ; Fiedler, J ; Thum, T ; Naumenko, VS ; Pandey, G ; Ponimaskin, E |
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Zeitschrift: | Nature communications, Jg. 10 (2019-09-02), Heft 1, S. 3924 |
Veröffentlichung: | [London] : Nature Pub. Group, 2019 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (electronic) |
DOI: | 10.1038/s41467-019-11876-5 |
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