Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action

Nature Neuroscience
Nadia M TsankovaEric J Nestler

Abstract

To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly increased repressive histone methylation at their corresponding promoters. Chronic imipramine reversed this downregulation and increased histone acetylation at these promoters. This hyperacetylation by chronic imipramine was associated with a selective downregulation of histone deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the hippocampus blocked imipramine's ability to reverse depression-like behavior. These experiments underscore an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression.

References

Aug 11, 1994·Nucleic Acids Research·S J ClarkM Frommer
Oct 12, 1999·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A Russo-NeustadtC W Cotman
Oct 4, 2000·Archives of General Psychiatry·R M Sapolsky
May 1, 2001·Nature Medicine·H K ManjiD S Charney
Jun 15, 2001·Laboratory Investigation; a Journal of Technical Methods and Pathology·J ChenA J Becker
Aug 11, 2001·Science·T Jenuwein, C D Allis
Apr 5, 2002·Neuron·Eric J NestlerLisa M Monteggia
Jun 18, 2002·Current Opinion in Cell Biology·Monika Lachner, Thomas Jenuwein
Jun 22, 2002·Pharmacology, Biochemistry, and Behavior·Eberhard Fuchs, Gabriele Flügge
Aug 8, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michel BarrotEric J Nestler
Oct 26, 2002·Science·Victoria V LunyakMichael G Rosenfeld
Nov 7, 2002·Cell·Bryan M Turner
Dec 17, 2002·Nature·Jean-Pierre EtchegaraySteven M Reppert
Jan 24, 2003·Nature·Gary Felsenfeld, Mark Groudine
Feb 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emma HocklyGillian P Bates
May 6, 2003·Journal of Cell Science·Monika LachnerThomas Jenuwein
Aug 6, 2003·The American Journal of Psychiatry·Yvette I ShelineHelena C Kraemer
Sep 5, 2003·Physiology & Behavior·Eberhard Fuchs, Gabriele Flügge
Sep 13, 2003·Journal of Neurochemistry·Masataka HoshinoHitoshi Okazawa
Jun 5, 2004·European Psychiatry : the Journal of the Association of European Psychiatrists·B S McEwenL P Reagan
Jun 18, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nadia M TsankovaEric J Nestler
Jun 29, 2004·Nature Neuroscience·Ian C G WeaverMichael J Meaney
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Lisa M MonteggiaEric J Nestler
Jul 24, 2004·Biological Psychiatry·Ronald S Duman
Jul 27, 2004·The Journal of Biological Chemistry·Jonathan M LevensonJ David Sweatt
Sep 24, 2004·Current Opinion in Genetics & Development·Jenny Hsieh, Fred H Gage
Dec 2, 2004·Frontiers in Neuroendocrinology·Lucia Tapia-ArancibiaSandor Arancibia
Dec 29, 2004·Cell·Stefan Kubicek, Thomas Jenuwein
Jan 18, 2005·Neuroscience and Biobehavioral Reviews·Bauke BuwaldaJaap M Koolhaas
Jan 18, 2005·Nature Reviews. Neuroscience·Jonathan M Levenson, J David Sweatt

❮ Previous
Next ❯

Citations

May 21, 2013·Cellular and Molecular Life Sciences : CMLS·Jenny Tung, Yoav Gilad
Jan 26, 2011·Der Nervenarzt·G PaslakisM Deuschle
Oct 22, 2009·Virchows Archiv : an International Journal of Pathology·Andrew P Feinberg
Apr 26, 2012·Brain Structure & Function·Zhi-Gang YaoChuan Qin
Mar 26, 2013·Cell and Tissue Research·Olivia F O'Leary, John F Cryan
Mar 28, 2013·Cell and Tissue Research·Francis Chaouloff
May 28, 2013·Cell and Tissue Research·Raffaella MolteniMarco A Riva
Jan 12, 2012·Bulletin of Experimental Biology and Medicine·M Kh SalimgareevaS B Seredenin
Feb 7, 2012·Current Psychiatry Reports·Chris Murgatroyd, Dietmar Spengler
Jun 29, 2011·Journal of Molecular Neuroscience : MN·Renata SuchanekJan Kowalski
Jul 14, 2011·Journal of Molecular Neuroscience : MN·Xin LiBaoxue Yang
Nov 20, 2012·Molecular Neurobiology·Céline Pattaroni, Claire Jacob
Jan 1, 2008·Environmental Health and Preventive Medicine·Patrick O McGowan, Tadafumi Kato
Jan 1, 2008·Environmental Health and Preventive Medicine·Takeo Kubota
Jul 24, 2010·Neuroscience Bulletin·Hua-Cheng YanTian-Ming Gao
Apr 15, 2010·Neurotoxicity Research·Robert M Post
Oct 5, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Melissa Mahgoub, Lisa M Monteggia
Mar 1, 2014·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·J CorralesK L Willett
Apr 15, 2010·Neuron Glia Biology·Melanie JawerkaMagdalena Götz
Aug 26, 2010·Journal of Proteome Research·Mariana D Plazas-Mayorca, Kent E Vrana
Dec 7, 2010·Acta Pharmacologica Sinica·Hui Yu, Zhe-yu Chen
May 2, 2012·Molecular Psychiatry·J P LopezG Turecki

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Herbert E CovingtonEric J Nestler
Nature Reviews. Neuroscience
Nadia M TsankovaEric J Nestler
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Matthew B WilkinsonEric J Nestler
© 2021 Meta ULC. All rights reserved