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

Gorinski, Nataliya (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Bijata, Monika (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany / Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland
Prasad, Sonal, 1988- (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
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Wirth, Alexander (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Abdel Galil, Dalia (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Zeug, Andre (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, German
Bazovkina, Daria (author)
Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia
Kondaurova, Elena (author)
Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia
Kulikova, Elizabeth (author)
Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia
Ilchibaeva, Tatiana (author)
Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia
Zareba-Koziol, Monika (author)
Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland
Papaleo, Francesco (author)
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy
Scheggia, Diego (author)
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy
Kochlamazashvili, Gaga (author)
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy
Dityatev, Alexander (author)
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy / Molecular Neuroplasticity, DZNE, Leipziger Str. 44, 39120, Magdeburg, Germany
Smyth, Ian (author)
Anatomy & Developmental Biology, Monash University, 3800, Melbourne, Australia
Krzystyniak, Adam (author)
Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland
Wlodarczyk, Jakub (author)
Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland
Richter, Diethelm W. (author)
Neuro and Sensory Physiology, University of Göttingen, 37073, Göttingen, Germany
Strekalova, Tatyana (author)
Sechenov First Moscow State Medical University, Moscow, Russia / Neuroscience, Maastricht University, 6229 ER, Maastricht, Netherlands / Laboratory of Psychiatric Neurobiology and Institute of General Pathology and Pathophysiology, Sechenov First Moscow State Medical University, Trubetskaya 8, 119315, Moscow, Russia
Sigrist, Stephan (author)
Institute of Biology, Free University Berlin, Takustr. 6, 14195, Berlin, Germany
Bang, Claudia (author)
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Hobuß, Lisa (author)
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Fiedler, Jan (author)
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Thum, Thomas (author)
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
Naumenko, Vladimir S. (author)
Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia
Pandey, Ghanshyam (author)
Department of Psychiatry, University of Illinois, 1601 W. Taylor Street, Chicago, IL, 60612, USA
Ponimaskin, Evgeni (author)
Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
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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 (creator_code:org_t)
2019-09-02
2019
English.
In: Nature Communications. - : Nature Communications. - 2041-1723. ; 10:1, s. 1-14
Related links:
https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

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