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.neures.2009.09.367

Cited by 29 publications

(53 citation statements)

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“…To date, epigenetic modifications, such as DNA methylation and posttransalational histone modifications have been suggested in some psychiatric phenotypes, including schizophrenia, bipolar disorder, and suicide [61,62,63]. Of particular interest is DNA methylation, a process in which cystosine nucleotides are methylated with the aid of DNA methyltransferases (DNMTs).…”

Section: -Future Methods To Study the Effect Of Polyamines In Suicidementioning

confidence: 99%

Suicide and the Polyamine System

Gross¹,

Turecki

2013

CNSNDDT

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Suicide is a significant worldwide public health problem. Understanding the neurobiology is important as it can help us to better elucidate underlying etiological factors and provide opportunities for intervention. In recent years, many lines of research have suggested that the polyamine system may be dysregulated in suicidal behaviors. Initial research in animals provided evidence of a dysfunctional polyamine stress response system, while later work using post-mortem human brain tissue has suggested that molecular mechanisms may be at play in the suicide brain. In this review, we will describe the research that suggests the presence of alterations in the polyamine system in mental disorders and behavioral phenotypes, with particular attention to work on suicide. In addition, we will also describe potential avenues for future work. KeywordsEpigenetics; Major Depressive Disorder; Neurobiology; Polyamines; Polyamine Stress Response; Spermidine/Spermine-N 1 -Acetyltransferase; Suicide -IntroductionSuicide, most often associated with major depressive disorder (MDD) [1], is an important cause of premature death around the world [2]. According to the World Health Organization (www.who.int, 2012), approximately one million people die by suicide annually, and the rate of suicide attempts is 20 times greater than that of suicide completion (www.who.int, 2012). As such, suicidal behaviors (SB) are an important source of public health concern. The etiology of suicide is complex [3], and commonly understood as resulting from the interaction of predisposing (distal) and precipitant (proximal) factors [4]. Biological alterations resulting from a combination of genetic and environmental risk factors underlie predisposition to suicide, but the exact molecular mechanisms at play remain largely unclear. As such, it is important that we gain a better understanding of the molecular processes associated with suicide in order to identify new avenues for prevention and intervention.Over the past several decades, molecular studies of suicide and MDD have focused on the monoamine system. Beginning in the late 1960s, research into the neurobiology of suicide

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Section: -Future Methods To Study the Effect Of Polyamines In Suicidementioning

confidence: 99%

Suicide and the Polyamine System

Gross¹,

Turecki

2013

CNSNDDT

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Section: Reviewmentioning

confidence: 99%

“…One study found that HDAC2 and HDAC5 were increased in patients in their depressive but not remitted state, whereas HDAC6 and HDAC8 were decreased in patients regardless of their states, and HDAC4 was increased in the depressive state of bipolar patients (Hobara et al, 2010). Studies in mice suggest that these changes are unlikely due to antidepressant treatment (Hobara et al, 2010). The induction of HDACs 2/5 and 4 in unipolar and bipolar patients, respectively, only in the depressive state suggests that these changes may be associated with depression symptoms rather than adaptive responses, and agree with the general consensus (albeit with some exceptions) that histone acetylation in brain has a pro-adaptive role in stress and depression.…”

Section: Reviewmentioning

confidence: 99%

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Sun

Kennedy

Nestler

2012

Neuropsychopharmacol

347

233

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Major depressive disorder is a chronic, remitting syndrome involving widely distributed circuits in the brain. Stable alterations in gene expression that contribute to structural and functional changes in multiple brain regions are implicated in the heterogeneity and pathogenesis of the illness. Epigenetic events that alter chromatin structure to regulate programs of gene expression have been associated with depression-related behavior, antidepressant action, and resistance to depression or 'resilience' in animal models, with increasing evidence for similar mechanisms occurring in postmortem brains of depressed humans. In this review, we discuss recent advances in our understanding of epigenetic contributions to depression, in particular the role of histone acetylation and methylation, which are revealing novel mechanistic insight into the syndrome that may aid in the development of novel targets for depression treatment.

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“…Post-translational histone modifications and DNA methylation are examples of epigenetic mechanisms that modify gene expression without altering the DNA sequence (Nestler, 2009). To date, epigenetic modifications have been implicated in several psychiatric phenotypes, including schizophrenia (Akbarian et al, 2005), bipolar disorder (Hobara et al, 2010), and suicide . Recently, our group found a significant increase in trimethylated histone 3-lysine 4 (H3K4me3), a marker of open chromatin, in suicide completers for OAZ1, and the levels of this modification were significantly correlated with expression of this gene (Fiori, Gross, & Turecki, 2011b).…”

Section: Introductionmentioning

confidence: 99%

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

Gross

Fiori

Labonté

et al. 2013

Journal of Psychiatric Research

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Suicide is among the leading causes of death worldwide. The polyamine system has been increasingly implicated in the neurobiology of suicide. Previous research has indicated that epigenetic mechanisms play a role in explaining dysregulation of polyamine genes in suicide completers. Nevertheless, regulatory mechanisms explaining polyamine biosynthetic genes displaying dysregulated expression in suicide completers, including ornithine decarboxylase antizymes 1 and 2 (OAZ1 and OAZ2), S-adenosylmethionine decarboxylase (AMD1), and arginase 2 (ARG2), have yet to be elucidated. In this study, we investigated methylation patterns in the promoter region of OAZ1, OAZ2, AMD1, and ARG2 in Brodmann area 44 from a group of 33 suicide completers and 31 non-suicide controls. We found significant site-specific differences in methylation in the promoter of ARG2 and AMD1 that were also significantly negatively correlated with gene expression. These findings provide further support for a role for the involvement of epigenetic modifications in the regulation of genes associated with polyamine biosynthesis, and which may contribute to the complexity of suicidal behaviors.

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Altered gene expression of histone deacetylases in mood disorder patients

Cited by 29 publications

References 0 publications

Suicide and the Polyamine System

Suicide and the Polyamine System

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

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