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Stress, epigenetics, and alcoholism.

Moonat S, Pandey SC - Alcohol Res (2012)

Bottom Line: Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders.Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria.Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes.

View Article: PubMed Central - PubMed

Affiliation: University of Illinois, Chicago, IL, USA.

ABSTRACT
Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism.

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Related in: MedlinePlus

The coordinated actions of proteins involved in epigenetic modifications that regulate gene transcriptional processes. During the 3rst step in the conversion of genetic information encoded in the DNA into gene products (i.e., during gene transcription), the DNA to be transcribed is associated with histone proteins (light blue) that are modified by the addition of acetyl groups (green). This modification results in a relaxed chromatin configuration that allows the transcriptional machinery access to the DNA. Enzymes, DNA methyltransferases (DNMTs), can add methyl groups (red) to the DNA at certain sequences of DNA building blocks (i.e., CpG islands). This methylation causes recruitment of methyl binding domain (MBD) protein complexes that also include repressor proteins, such as histone deacetylases (HDAC). The HDACs remove acetyl groups from histone proteins, resulting in a condensed chromatin that limits the binding of the transcriptional machinery, thereby decreasing gene transcription. Thus, activation of both DNMT and HDAC causes a reduction in gene transcription. Treatment with DNMT inhibitors and HDAC inhibitors may block these enzymatic processes and return the chromatin to a relaxed state, allowing gene transcription.
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f2-arcr-34-4-495: The coordinated actions of proteins involved in epigenetic modifications that regulate gene transcriptional processes. During the 3rst step in the conversion of genetic information encoded in the DNA into gene products (i.e., during gene transcription), the DNA to be transcribed is associated with histone proteins (light blue) that are modified by the addition of acetyl groups (green). This modification results in a relaxed chromatin configuration that allows the transcriptional machinery access to the DNA. Enzymes, DNA methyltransferases (DNMTs), can add methyl groups (red) to the DNA at certain sequences of DNA building blocks (i.e., CpG islands). This methylation causes recruitment of methyl binding domain (MBD) protein complexes that also include repressor proteins, such as histone deacetylases (HDAC). The HDACs remove acetyl groups from histone proteins, resulting in a condensed chromatin that limits the binding of the transcriptional machinery, thereby decreasing gene transcription. Thus, activation of both DNMT and HDAC causes a reduction in gene transcription. Treatment with DNMT inhibitors and HDAC inhibitors may block these enzymatic processes and return the chromatin to a relaxed state, allowing gene transcription.

Mentions: HDACs are enzymes that can remove acetyl groups from histone proteins; they seem to be key elements in the regulation of chromatin structure and function (figure 2) (Jenuwein and Allis 2001). Inhibition of HDAC enzymes by pharmacological intervention is effective in the treatment of some have been approved or are in clinical trials for this purpose (Dokmanovic et al. 2007; Lane and Chabner 2009). Recently, HDAC inhibitors also have been explored as potential therapeutic agents in the treatment of psychiatric disorders, including stress-related disorders and addiction, and have become an important focus of research in the neuroscience field (Covington et al. 2009; Kumar et al. 2005; Pandey et al. 2008a; Renthal and Nestler 2008; Tsankova et al. 2007). Several HDAC isoforms have been identified and grouped into four classes based upon their regulation and cellular localization (de Ruijter et al. 2003; Dokmanovic et al. 2007). Specific HDAC variants (i.e., isoforms) recently have been identified as regulators of neuronal processes such as synaptic plasticity (Guan et al. 2009; Renthal and Nestler 2008). This suggests that use of isoform-specific HDAC inhibitors may increase the specificity and efficacy of these drugs in the treatment of psychiatric disorders.


Stress, epigenetics, and alcoholism.

Moonat S, Pandey SC - Alcohol Res (2012)

The coordinated actions of proteins involved in epigenetic modifications that regulate gene transcriptional processes. During the 3rst step in the conversion of genetic information encoded in the DNA into gene products (i.e., during gene transcription), the DNA to be transcribed is associated with histone proteins (light blue) that are modified by the addition of acetyl groups (green). This modification results in a relaxed chromatin configuration that allows the transcriptional machinery access to the DNA. Enzymes, DNA methyltransferases (DNMTs), can add methyl groups (red) to the DNA at certain sequences of DNA building blocks (i.e., CpG islands). This methylation causes recruitment of methyl binding domain (MBD) protein complexes that also include repressor proteins, such as histone deacetylases (HDAC). The HDACs remove acetyl groups from histone proteins, resulting in a condensed chromatin that limits the binding of the transcriptional machinery, thereby decreasing gene transcription. Thus, activation of both DNMT and HDAC causes a reduction in gene transcription. Treatment with DNMT inhibitors and HDAC inhibitors may block these enzymatic processes and return the chromatin to a relaxed state, allowing gene transcription.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860391&req=5

f2-arcr-34-4-495: The coordinated actions of proteins involved in epigenetic modifications that regulate gene transcriptional processes. During the 3rst step in the conversion of genetic information encoded in the DNA into gene products (i.e., during gene transcription), the DNA to be transcribed is associated with histone proteins (light blue) that are modified by the addition of acetyl groups (green). This modification results in a relaxed chromatin configuration that allows the transcriptional machinery access to the DNA. Enzymes, DNA methyltransferases (DNMTs), can add methyl groups (red) to the DNA at certain sequences of DNA building blocks (i.e., CpG islands). This methylation causes recruitment of methyl binding domain (MBD) protein complexes that also include repressor proteins, such as histone deacetylases (HDAC). The HDACs remove acetyl groups from histone proteins, resulting in a condensed chromatin that limits the binding of the transcriptional machinery, thereby decreasing gene transcription. Thus, activation of both DNMT and HDAC causes a reduction in gene transcription. Treatment with DNMT inhibitors and HDAC inhibitors may block these enzymatic processes and return the chromatin to a relaxed state, allowing gene transcription.
Mentions: HDACs are enzymes that can remove acetyl groups from histone proteins; they seem to be key elements in the regulation of chromatin structure and function (figure 2) (Jenuwein and Allis 2001). Inhibition of HDAC enzymes by pharmacological intervention is effective in the treatment of some have been approved or are in clinical trials for this purpose (Dokmanovic et al. 2007; Lane and Chabner 2009). Recently, HDAC inhibitors also have been explored as potential therapeutic agents in the treatment of psychiatric disorders, including stress-related disorders and addiction, and have become an important focus of research in the neuroscience field (Covington et al. 2009; Kumar et al. 2005; Pandey et al. 2008a; Renthal and Nestler 2008; Tsankova et al. 2007). Several HDAC isoforms have been identified and grouped into four classes based upon their regulation and cellular localization (de Ruijter et al. 2003; Dokmanovic et al. 2007). Specific HDAC variants (i.e., isoforms) recently have been identified as regulators of neuronal processes such as synaptic plasticity (Guan et al. 2009; Renthal and Nestler 2008). This suggests that use of isoform-specific HDAC inhibitors may increase the specificity and efficacy of these drugs in the treatment of psychiatric disorders.

Bottom Line: Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders.Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria.Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes.

View Article: PubMed Central - PubMed

Affiliation: University of Illinois, Chicago, IL, USA.

ABSTRACT
Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism.

Show MeSH
Related in: MedlinePlus