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BDNF, HDAC, depression

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https://www.readbyqxmd.com/read/26970016/the-hdac-inhibitor-saha-improves-depressive-like-behavior-of-crtc1-deficient-mice-possible-relevance-for-treatment-resistant-depression
#1
Elsa M Meylan, Olivier Halfon, Pierre J Magistretti, Jean-René Cardinaux
Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine...
August 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26890656/gestational-stress-induces-depressive-like-and-anxiety-like-phenotypes-through-epigenetic-regulation-of-bdnf-expression-in-offspring-hippocampus
#2
Yu Zheng, Weidong Fan, Xianquan Zhang, Erbo Dong
Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation...
2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/26433268/chronic-stress-and-antidepressant-induced-changes-in-hdac5-and-sirt2-affect-synaptic-plasticity
#3
M Erburu, I Muñoz-Cobo, J Domínguez-Andrés, E Beltran, T Suzuki, A Mai, S Valente, E Puerta, R M Tordera
Changes in histone acetylation could contribute to the pathogenesis of depression and antidepressant therapy. Using the chronic social defeat stress (CSDS) model of depression and different antidepressant treatments we studied the regulation of histone deacetylases (Hdac׳s) and synaptic plasticity markers in the prefrontal cortex (PFC). Further, functional implication of identified Hdac׳s in brain plasticity was explored. Mice were exposed to CSDS (10 days) followed by saline or imipramine (4 weeks). PFC Hdac׳s mRNA abundance was studied and compared to human׳s...
November 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26171219/antidepressant-activity-of-fingolimod-in-mice
#4
Luigi di Nuzzo, Rosamaria Orlando, Cristina Tognoli, Paola Di Pietro, Giuseppe Bertini, Jessica Miele, Domenico Bucci, Marta Motolese, Sergio Scaccianoce, Alessandra Caruso, Gianluca Mauro, Carmine De Lucia, Giuseppe Battaglia, Valeria Bruno, Paolo Francesco Fabene, Ferdinando Nicoletti
Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity...
June 2015: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/25639887/an-hdac-dependent-epigenetic-mechanism-that-enhances-the-efficacy-of-the-antidepressant-drug-fluoxetine
#5
C Schmauss
Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25233278/sodium-butyrate-functions-as-an-antidepressant-and-improves-cognition-with-enhanced-neurotrophic-expression-in-models-of-maternal-deprivation-and-chronic-mild-stress
#6
Samira Silva Valvassori, Roger Bitencourt Varela, Camila Orlandi Arent, Gustavo Colombo Dal-Pont, Tamara Sarate Bobsin, Josiane Budni, Gislaine Zilli Reus, Joao Quevedo
It is known that cognitive processes, such as learning and memory, are affected in depression. Several authors have described histone deacetylase (HDAC) inhibitors as a class of drugs that improves long-term memory formation. The current study examined the effects of maternal deprivation (MD) and chronic mild stress (CMS), which have been shown as animal models of depression, and the effects of sodium butyrate (SB), a HDAC inhibitor, on recognition memory. Considering that neurotrophic factors has been pointed as a key event involved with cognition and depressive disorder, levels of neurotrophic factors (BDNF, NGF and GDNF) were also investigated...
2014: Current Neurovascular Research
https://www.readbyqxmd.com/read/24607816/possible-additional-antidepressant-like-mechanism-of-sodium-butyrate-targeting-the-hippocampus
#7
Arum Han, Yu-Bin Sung, Soo-Young Chung, Min-Soo Kwon
Chromatin remodeling mediated by histone acetylation might be involved in the pathophysiology and the treatment of depression. Recently, it has been reported that the histone deacetylase (HDAC) inhibitors, such as sodium butyrate (SB), could be a potential therapeutic agent for depression treatment. In the present study, we aimed to clarify the antidepressant mechanism of SB in the hippocampus. The mice were exposed to chronic restraint stress (CRS) for 14 consecutive days (2 h/day) to induce depression-like behaviors...
June 2014: Neuropharmacology
https://www.readbyqxmd.com/read/23706065/novel-routes-to-bipolar-disorder-drug-discovery
#8
REVIEW
Nicolas Hoertel, Pierre de Maricourt, Philip Gorwood
INTRODUCTION: Bipolar disorder (BD) is a severe and chronic medical condition typified by episodic recurrent mania (or hypomania) in addition to major depression. BD is associated with a number of negative outcomes including premature death, reduced quality of life and can also lead to other complications including impaired cognitive function. Unfortunately, the currently available pharmacological treatments for BD are insufficient for many with the condition. AREAS COVERED: This review focuses on known therapeutic targets of mood stabilizing drugs including: the glycogen synthase kinase-3 (GSK-3), the phosphoinositide pathway and protein kinase C (PKC), the brain-derived neurotrophic factor (BDNF), and histone deacetylases (HDACs)...
August 2013: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/23093383/modulation-of-neuronal-plasticity-following-chronic-concomitant-administration-of-the-novel-antipsychotic-lurasidone-with-the-mood-stabilizer-valproic-acid
#9
F Calabrese, A Luoni, G Guidotti, G Racagni, F Fumagalli, M A Riva
RATIONALE: Combinatory therapy is widely used in psychiatry owing to the possibility that drugs with different mechanisms of action may synergize to improve functions deteriorated in schizophrenia, bipolar disorders, and major depression. While combinatory strategies rely on receptor and synaptic mechanisms, it should also be considered that two drugs may also "interact" on the long-term to determine more robust changes in neuronal plasticity, which represents a downstream target important for functional recovery...
March 2013: Psychopharmacology
https://www.readbyqxmd.com/read/21179661/-epigenetic-mechanism-of-depression
#10
Shigeru Morinobu, Manabu Fuchikami, Yosuke Yamawaki, Shigeto Yamamoto, Akiko Kurata, Shigeto Yamawaki
Numerous epigenetic studies have revealed that the acetylated status of histone as well as methylated status of cytosine is closely involved in gene transcription. Preclinical and clinical studies demonstrate that changes in levels of various genes in the brain including BDNF, play a role in the pathophysiology of depression. It is well known that the levels of BDNF mRNA and protein in the rat brain, such as frontal cortex and hippocampus, was decreased in response to stress, but the precise mechanism of stress-induced downregulation of BDNF has yet to be characterized...
2010: Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica
https://www.readbyqxmd.com/read/19360904/histone-deacetylase-inhibitors-promote-neurosteroid-mediated-cell-differentiation-and-enhance-serotonin-stimulated-brain-derived-neurotrophic-factor-gene-expression-in-rat-c6-glioma-cells
#11
Kyoji Morita, Takako Gotohda, Hideki Arimochi, Mi-Sook Lee, Song Her
Progesterone treatment has previously been reported to promote the differentiation of glial cells probably through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain and hence has been suggested to improve mood disorders and other symptoms in depressive patients. Based on these previous observations, the effects on glial cells of histone deacetylase (HDAC) inhibitors, which are known as agents promoting cell differentiation, were examined using rat C6 glioma cells as a model for in vitro studies...
August 15, 2009: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/17925795/the-mood-stabilizers-lithium-and-valproate-selectively-activate-the-promoter-iv-of-brain-derived-neurotrophic-factor-in-neurons
#12
S Yasuda, M-H Liang, Z Marinova, A Yahyavi, D-M Chuang
Brain-derived neurotrophic factor (BDNF) has been strongly implicated in the synaptic plasticity, neuronal survival and pathophysiology of depression. Lithium and valproic acid (VPA) are two primary mood-stabilizing drugs used to treat bipolar disorder. Treatment of cultured rat cortical neurons with therapeutic concentrations of LiCl or VPA selectively increased the levels of exon IV (formerly rat exon III)-containing BDNF mRNA, and the activity of BDNF promoter IV. Surprisingly, lithium- or VPA-responsive element(s) in promoter IV resides in a region upstream from the calcium-responsive elements (CaREs) responsible for depolarization-induced BDNF induction...
January 2009: Molecular Psychiatry
https://www.readbyqxmd.com/read/16501568/sustained-hippocampal-chromatin-regulation-in-a-mouse-model-of-depression-and-antidepressant-action
#13
Nadia M Tsankova, Olivier Berton, William Renthal, Arvind Kumar, Rachel L Neve, Eric J Nestler
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...
April 2006: Nature Neuroscience
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