Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes

Ookubo, Masanori; Kanai, Hirohiko; Aoki, Harusuke; Yamada, Naoto

doi:10.1016/j.jpsychires.2013.05.028

Cited by 46 publications

(46 citation statements)

References 37 publications

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“…However, our results suggest that imipramine can contribute to the regulation of target genes, such as BDNF and NR2B, by regulating histone acetylation. It has also been reported that expression of HDAC2/3/5 can increase in the mouse brain following treatment with antidepressants, such as sodium valproate and lithium chloride, and that this effect can differ between brain regions (Ookubo et al, 2013). These discrepancies suggest that imipramine's effects on HDACs may depend on the type of study (in vivo or in vitro), material studied (cultured neuron or brain tissue), brain region, and the antidepressant tested.…”

Section: Discussionmentioning

confidence: 99%

Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Nghia

Hirasawa

Kasai

et al. 2015

European Journal of Pharmacology

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Imipramine, a major antidepressant, is known to inhibit reuptake of serotonin and norepinephrine, which contributes to recovery from major depressive disorder. It has recently been reported that acute imipramine treatment inhibits N-methyl-d-aspartate (NMDA) receptor activity. However, the mechanisms underlying long-term effects of imipramine have not been identified. We tested these distinct effects in mouse cortical neurons and found that acute (30s) imipramine treatment decreased Ca(2+) influx through NMDA receptors, whereas long-term treatment (48h) increased Ca(2+) influx via the same receptors. Furthermore, long-term treatment increased NMDA receptor 2B (NR2B) subunit expression via epigenetic changes, including increased acetylation of histones H3K9 and H3K27 in the NR2B promoter and decreased activity of histone deacetylase 3 (HDAC3) and HDAC4. These results suggest that the long-term effects of imipramine on NMDA receptors are quite different from its acute effects. Furthermore, increased NR2B expression via epigenetic alterations might be a part of the mechanism responsible for this long-term effect.

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Section: Discussionmentioning

confidence: 99%

Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Nghia

Hirasawa

Kasai

et al. 2015

European Journal of Pharmacology

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“…One of the most comprehensive reports on the effects of antidepressants and mood stabilizers on HDAC gene expression is by Ookubo et al (2013). In different areas of the brain of C57Bl6 mice, these authors have observed region-specific effects of commonly prescribed drugs on histone H3 acetylation (AcH3) and HDAC gene expression.…”

Section: Stress Depression and Schizophreniamentioning

confidence: 99%

“…In different areas of the brain of C57Bl6 mice, these authors have observed region-specific effects of commonly prescribed drugs on histone H3 acetylation (AcH3) and HDAC gene expression. There is a significant increase of histone H3 acetylation in the nucleus accumbens after 15 days of treatment with sodium valproate, lithium chloride, lamotrigine, levetiracetam, olanzapine, clozapine, clomipramine, (S)-citalopram oxalate, or duloxetine hydrochloride (Ookubo et al, 2013). In the striatum, treatment with clomipramine, (S)-citalopram oxalate, duloxetine hydrochloride, mirtazapine, carbamazepine, lamotrigine, levetiracetam, olanzapine, or clozapine results in significant increases of both HDAC2 and HDAC3 expression (Ookubo et al, 2013).…”

Section: Stress Depression and Schizophreniamentioning

confidence: 99%

“…There is a significant increase of histone H3 acetylation in the nucleus accumbens after 15 days of treatment with sodium valproate, lithium chloride, lamotrigine, levetiracetam, olanzapine, clozapine, clomipramine, (S)-citalopram oxalate, or duloxetine hydrochloride (Ookubo et al, 2013). In the striatum, treatment with clomipramine, (S)-citalopram oxalate, duloxetine hydrochloride, mirtazapine, carbamazepine, lamotrigine, levetiracetam, olanzapine, or clozapine results in significant increases of both HDAC2 and HDAC3 expression (Ookubo et al, 2013). In the cingulate cortex, clomipramine, mirtazapine, sodium valproate, carbamazepine, lamotrigine, levetiracetam, olanzapine, or clozapine significantly increases HDAC3 expression.…”

Section: Stress Depression and Schizophreniamentioning

confidence: 99%

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Histone deacetylases (HDACs) and brain function

2015

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Modulation of gene expression is a constant and necessary event for mammalian brain function. An important way of regulating gene expression is through the remodeling of chromatin, the complex of DNA, and histone proteins around which DNA wraps. The "histone code hypothesis" places histone post-translational modifications as a significant part of chromatin remodeling to regulate transcriptional activity. Acetylation of histones by histone acetyl transferases and deacetylation by histone deacetylases (HDACs) at lysine residues are the most studied histone post-translational modifications in cognition and neuropsychiatric diseases. Here, we review the literature regarding the role of HDACs in brain function. Among the roles of HDACs in the brain, studies show that they participate in glial lineage development, learning and memory, neuropsychiatric diseases, and even rare neurologic diseases. Most HDACs can be targeted with small molecules. However, additional brain-penetrant specific inhibitors with high central nervous system exposure are needed to determine the cause-and-effect relationship between individual HDACs and brain-associated diseases.

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“…At present, it is thought that these effects of VPA on gene expression could contribute to the long-term therapeutic effects of VPA in BD, whereas the acute therapeutic effects could be due to biochemical/physiological effects of VPA such as enhancement of GABAergic neurotransmission [67]. Other currently used psychotropic drugs which have been shown to have a HDACi effect in the brain in preclinical studies include lithium, levetiracetam, olanzapine, clomipramine and clozapine [69]. Some currently used psychotropic drugs have been found to exert epigenetic effects other than HDACi effects.…”

Section: Epigenetic Effects Of Currently Used Drugs For Bdmentioning

confidence: 99%

Epigenetic approaches for bipolar disorder drug discovery

Peedicayil

2014

Expert Opinion on Drug Discovery

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HDACis have shown promising results in preclinical studies of BD. However, the currently available HDACis suffer from acting non-specifically on HDAC isozymes. More isozyme-specific HDACis are likely to have greater efficacy and less toxicity than the current HDACis. It is suggested that efforts should be made to develop such HDACis. Once such HDACis with adequate ability to cross the blood-brain barrier become available, investigators could consider proceeding to clinical trials of HDACis for the treatment of BD.

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Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes

Cited by 46 publications

References 37 publications

Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

Histone deacetylases (HDACs) and brain function

Epigenetic approaches for bipolar disorder drug discovery

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