Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
Articolo
Data di Pubblicazione:
2019
Citazione:
Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors / N. Gorinski, M. Bijata, S. Prasad, A. Wirth, D. Abdel Galil, A. Zeug, D. Bazovkina, E. Kondaurova, E. Kulikova, T. Ilchibaeva, M. Zareba-Koziol, F. Papaleo, D. Scheggia, G. Kochlamazashvili, A. Dityatev, I. Smyth, A. Krzystyniak, J. Wlodarczyk, D.W. Richter, T. Strekalova, S. Sigrist, C. Bang, L. Hobuss, J. Fiedler, T. Thum, V.S. Naumenko, G. Pandey, E. Ponimaskin. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019 Dec 01).
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Acyltransferases; Animals; Brain; Cell Line, Tumor; Depression; Depressive Disorder, Major; Gene Expression Regulation; Humans; Lipoylation; Male; Mice, Inbred C57BL; MicroRNAs; Rats, Wistar; Receptor, Serotonin, 5-HT1A
Elenco autori:
N. Gorinski, M. Bijata, S. Prasad, A. Wirth, D. Abdel Galil, A. Zeug, D. Bazovkina, E. Kondaurova, E. Kulikova, T. Ilchibaeva, M. Zareba-Koziol, F. Papaleo, D. Scheggia, G. Kochlamazashvili, A. Dityatev, I. Smyth, A. Krzystyniak, J. Wlodarczyk, D.W. Richter, T. Strekalova, S. Sigrist, C. Bang, L. Hobuss, J. Fiedler, T. Thum, V.S. Naumenko, G. Pandey, E. Ponimaskin
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