학술논문
Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors.
Document Type
Academic Journal
Author
Gorinski N; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Bijata M; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.; Prasad S; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Wirth A; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Abdel Galil D; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Zeug A; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Bazovkina D; Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.; Kondaurova E; Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.; Kulikova E; Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.; Ilchibaeva T; Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia.; Zareba-Koziol M; Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.; Papaleo F; Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.; Scheggia D; Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.; Kochlamazashvili G; Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.; Dityatev A; Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163, Genova, Italy.; Molecular Neuroplasticity, DZNE, Leipziger Str. 44, 39120, Magdeburg, Germany.; Smyth I; Anatomy & Developmental Biology, Monash University, 3800, Melbourne, Australia.; Krzystyniak A; Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.; Wlodarczyk J; Cell Biophysics, Nencki Institute, Pasteur Str. 3, 02-093, Warsaw, Poland.; Richter DW; Neuro and Sensory Physiology, University of Göttingen, 37073, Göttingen, Germany.; Strekalova T; 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 S; Institute of Biology, Free University Berlin, Takustr. 6, 14195, Berlin, Germany.; Bang C; Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Hobuß L; Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Fiedler J; Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Thum T; Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Naumenko VS; Behavioural Neurogenomics, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia. naumenko2002@mail.ru.; Pandey G; Department of Psychiatry, University of Illinois, 1601 W. Taylor Street, Chicago, IL, 60612, USA. GPandey@psych.uic.edu.; Ponimaskin E; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany. Ponimaskin.evgeni@mh-hannover.de.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.