Altered gene expression of histone deacetylases in mood disorder patients

Hobara, Teruyuki; Uchida, Shinichi; Otsuki, Koji; Matsubara, Takehiro; Funato, Hiromasa; Matsuo, Koji; Suetsugi, Masatomo; Watanabe, Yoshifumi

doi:10.1016/j.jpsychires.2009.08.015

Cited by 163 publications

(100 citation statements)

References 53 publications

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“…Moreover, a relevant study has demonstrated that Hdac5 over-expression blocks the behavioral effects of antidepressants in the CSDS model . Interestingly, an upregulation of cortical HDAC5 mRNA has been observed in subjects with major depressive disorder and bipolar disorder, compared to controls and patients in remission, supporting a clinical relevance for this change (Hobara et al, 2010). Yet, our human studies did not reveal significant changes in the mRNA expression of this enzyme.…”

Section: Functional Implication Of Hdac5 Regulationmentioning

confidence: 84%

“…Likewise, antidepressant therapy might be achieved in part via epigenetic mechanisms . Different epigenetic alterations have been observed in post-mortem tissue of depressed patients (Hobara et al, 2010) and of individuals who committed suicide (Keller et al, 2010). In addition, at the experimental level using animal models, stress and antidepressants induce chromatin modifications in limbic regions and induce stable changes in gene expression that affect different plasticity markers such as the brain derived neurotrophic factor (BDNF) and its upstream regulator cAMP response element binding protein (CREB) Wilkinson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect synaptic plasticity

Erburu

Muñoz-Cobo

Domínguez‐Andrés

et al. 2015

European Neuropsychopharmacology

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Section: Functional Implication Of Hdac5 Regulationmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect synaptic plasticity

Erburu

Muñoz-Cobo

Domínguez‐Andrés

et al. 2015

European Neuropsychopharmacology

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“…Recently, it was demonstrated that in major depressive disorder patients the expression of HDAC2 and -5 mRNA was increased in a depressive state, and in BD, the expression of HDAC4 mRNA was increased also in a depressive state, suggesting that changes in transcriptional regulation caused by the altered expression of HDACs is associated with the pathophysiology of mood disorders [22]. In an analysis of the National Brain Databank microarray collection, was observed that HDAC1 expression is increased in the prefrontal cortex of schizophrenia subjects [23].…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical Profile of Antimaniac Effects of Histone Deacetylases Inhibitors

et al. 2011

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An increasing number of studies have evaluated the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-field task. The activity of HDAC was evaluated in amygdala, striatum, prefrontal, and hippocampus of animals. The microinjection of SB and VPA in the ventricle, amygdala, striatum, and prefrontal, but not in hippocampus blocked the hyperactivity induced by m-AMPH. In addition, SB and VPA inhibited the HDAC activity; however, this effect varied depending on the experimental procedure and the brain structure evaluated. Our results suggest that the antimanic effects of SB and VPA, HDAC inhibitors, are related to the amygdala, striatum, and prefrontal, but not the hippocampus. More studies are needed to clarify the therapeutic effects of the HDAC inhibitor in BD and thereby develop new drugs.

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“…They further demonstrate that genetically reducing the availability of HDAC2 in mice resulted in attenuation of depression-like behavior due to exposure to stress. Both messenger RNA and protein expression of HDACs 1, 3, and 5 have been shown to be altered in depression, bipolar disorder, and schizophrenia (Benes et al, 2007;Covington et al, 2009;Hobara et al, 2010). Kurita et al (2012) report that the expression of HDAC2, but not HDAC1 or HDAC4, is elevated in the frontal cortex of schizophrenic patients treated with atypical antipsychotics (Rudenko and Tsai, 2014).…”

Section: Hdacs In Neuropsychiatric Diseasesmentioning

confidence: 99%

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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Altered gene expression of histone deacetylases in mood disorder patients

Cited by 163 publications

References 53 publications

Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect synaptic plasticity

Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect synaptic plasticity

Neuroanatomical Profile of Antimaniac Effects of Histone Deacetylases Inhibitors

Histone deacetylases (HDACs) and brain function

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