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Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany / Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.ORCID-id: 0000-0002-4455-5097
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
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2019 (Engelska)Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, nr 1, s. 1-14, artikel-id 3924Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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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Nature Communications , 2019. Vol. 10, nr 1, s. 1-14, artikel-id 3924
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Neurovetenskaper Farmaceutiska vetenskaper
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URN: urn:nbn:se:liu:diva-161244DOI: 10.1038/s41467-019-11876-5OAI: oai:DiVA.org:liu-161244DiVA, id: diva2:1365342
Tillgänglig från: 2019-10-24 Skapad: 2019-10-24 Senast uppdaterad: 2019-12-04Bibliografiskt granskad

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Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors(2006 kB)27 nedladdningar
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