Valproic Acid

Publication Title: 
L'Encephale

INTRODUCTION: Emotional reactivity and sleep constitute key dimensions of bipolar disorder. Emotional reactivity referred to emotion response intensity and emotion response threshold. Higher emotion reactivity is described during both mood episodes and periods of remission in bipolar disorder. As well, sleep disturbances are described during both acute episodes and euthymic periods in bipolar disorder. Links between sleep and emotion regulation start to be studied in general population.

Author(s): 
Boudebesse, Carole
Henry, Chantal
Publication Title: 
Nucleic Acids Research

Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple human cell types: neuroblastoma cells (SHSY5Y), neuronal precursor cells (NT2), differentiated neurons (hNT) and hepatoma cells (HepG2).

Author(s): 
Chen, Ying
Sharma, Rajiv P.
Costa, Robert H.
Costa, Erminio
Grayson, Dennis R.
Publication Title: 
Journal of Neurochemistry

Increased expression of 5-lipoxygenase is associated with various neuropathologies and may be related to epigenetic gene regulation. DNA methylation in promoter regions is typically associated with gene silencing. We found that human NT2 cells, which differentiate into neuron-like NT2-N cells, express 5-lipoxygenase and we investigated the relationship between 5-lipoxygenase expression and the methylation state of the 5-lipoxygenase core promoter.

Author(s): 
Zhang, Zhijing
Chen, Chang-qing
Manev, Hari
Publication Title: 
Journal of Psychiatric Research

OBJECTIVE: The emerging field of psychiatric epigenetics is constrained by the dearth of research methods feasible in living patients. With this focus, we report on two separate approaches, one in vitro and one in vivo, developed in our laboratory. METHOD: In the first approach, we isolated lymphocytes from 12 subjects and cultured their cells with either 0.7 mM valproic acid (VPA), 100 nM Trichostatin A (TSA), or DMSO (control) for 24h based upon previous dose response experiments.

Author(s): 
Gavin, David P.
Kartan, Saritha
Chase, Kayla
Jayaraman, Sundararajan
Sharma, Rajiv P.
Publication Title: 
Platelets

Both, the activity of transcription factors as well as epigenetic alterations in defined DNA regions regulate cellular differentiation processes. Hence, neuronal differentiation from neural progenitor cells is promoted by the transcription factor all trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid (VPA). VPA has also been shown to be involved in differentiation of tumor cells and to greatly improve the reprogramming of human somatic cells to induced pluripotent stem cells.

Author(s): 
Schweinfurth, N.
Hohmann, S.
Deuschle, M.
Lederbogen, F.
Schloss, P.
Publication Title: 
Progress in Neuro-Psychopharmacology & Biological Psychiatry

Valproate (VPA) is an anti-epileptic and mood-stabilizing drug with a broad range of action and which mechanism of action still remains in part elusive. Recently the discovery that VPA modifies the epigenome increasing the transcriptional rate of target genes raises the issue of understanding the exact role of this mechanism. In this work we tested the possibility that VPA could modify the epigenome of lymphomonocytes (PBMC) obtained from epileptic patients chronically treated in monotherapy with VPA and phenobarbital.

Author(s): 
Tremolizzo, Lucio
Difrancesco, Jacopo C.
Rodriguez-Menendez, Virginia
Riva, Chiara
Conti, Elisa
Galimberti, Gloria
Ruffmann, Claudio
Ferrarese, Carlo
Publication Title: 
Current Clinical Pharmacology

Valproic acid (VPA) is an anti-epileptic and mood-stabilizing compound successfully used in the clinics since many decades. During the last few years, research on VPA revitalized. VPA has profound impact on nuclear chromatin structure in target cells by impinging on epigenetic mechanisms such as inhibition of histone deacetylase HDAC1, with implications for HIV and cancer treatment, and for the direct reprogramming in generation of induced pluripotent stem (iPS) cells. VPA can thus act at multiple levels and in several cellular systems.

Author(s): 
Mazzoccoli, Gianluigi
Longhitano, Calogero
Vinciguerra, Manlio
Publication Title: 
European Archives of Psychiatry and Clinical Neuroscience

Notwithstanding the considerable advances in the treatment options for schizophrenia, the cognitive symptoms in particular are not receptive to antipsychotic treatment and considered one of the main predictors for poor social and functional outcome of the disease. Recent findings in preclinical model systems indicate that epigenetic modulation might emerge as a promising target for the treatment of cognitive disorders.

Author(s): 
Hasan, Alkomiet
Mitchell, Amanda
Schneider, Anja
Halene, Tobias
Akbarian, Schahram
Publication Title: 
The International Journal of Neuropsychopharmacology

Unraveling the epigenetic status of neuronal cells in the brain is critical to our understanding of the pathophysiology of psychiatric disorders, which may reflect a complex interaction between genetic and environmental factors. Several epigenetic studies of mood disorders have been conducted with postmortem brains. However, proper interpretation of the results is hampered by our scant understanding of the effects of mood stabilizers on the epigenetic status of neuronal cells.

Author(s): 
Asai, Tatsuro
Bundo, Miki
Sugawara, Hiroko
Sunaga, Fumiko
Ueda, Junko
Tanaka, Gen
Ishigooka, Jun
Kasai, Kiyoto
Kato, Tadafumi
Iwamoto, Kazuya
Publication Title: 
Bipolar Disorders

OBJECTIVES: Accumulating evidence implicates the potassium voltage-gated channel, KQT-like subfamily, member 2 and 3 (KCNQ2 and KCNQ3) genes in the etiology of bipolar disorder (BPD). Reduced KCNQ2 or KCNQ3 gene expression might lead to a loss of inhibitory M-current and an increase in neuronal hyperexcitability in disease. The goal of the present study was to evaluate epigenetic and gene expression associations of the KCNQ2 and KCNQ3 genes with BPD.

Author(s): 
Kaminsky, Zachary
Jones, Ilenna
Verma, Ranjana
Saleh, Lena
Trivedi, Hersh
Guintivano, Jerry
Akman, Ryan
Zandi, Peter
Lee, Richard S.
Potash, James B.

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