Epigenetic mechanisms of alcoholism and stress-related disorders

Palmisano, Martina; Pandey, Subhash C.

doi:10.1016/j.alcohol.2017.01.001

Cited by 89 publications

(60 citation statements)

References 176 publications

(246 reference statements)

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“…Substance abuse disorder is correlated with a stressful environment and stress increases the risk for relapse (Goldstein et al 2008). Furthermore, stress and addiction induce similar epigenetic and neurobiological modifications (Cadet 2016; Moonat and Pandey 2012; Palmisano and Pandey 2017; Spanagel et al 2014). Stress has an influence on the immune system (Stefanski 2000) and the immune system on the other hand is connected with pathways related to circadian rhythm (Dumbell et al 2016).…”

Section: Resultsmentioning

confidence: 99%

Animal models for bipolar disorder: from bedside to the cage

Beyer

Freund

2017

Int J Bipolar Disord

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Bipolar disorder is characterized by recurrent manic and depressive episodes. Patients suffering from this disorder experience dramatic mood swings with a wide variety of typical behavioral facets, affecting overall activity, energy, sexual behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased risk for suicide. Effective treatment options are limited and diagnosis can be complicated. To overcome these obstacles, a better understanding of the neurobiology underlying bipolar disorder is needed. Animal models can be useful tools in understanding brain mechanisms associated with certain behavior. The following review discusses several pathological aspects of humans suffering from bipolar disorder and compares these findings with insights obtained from several animal models mimicking diverse facets of its symptomatology. Various sections of the review concentrate on specific topics that are relevant in human patients, namely circadian rhythms, neurotransmitters, focusing on the dopaminergic system, stressful environment, and the immune system. We then explain how these areas have been manipulated to create animal models for the disorder. Even though several approaches have been conducted, there is still a lack of adequate animal models for bipolar disorder. Specifically, most animal models mimic only mania or depression and only a few include the cyclical nature of the human condition. Future studies could therefore focus on modeling both episodes in the same animal model to also have the possibility to investigate the switch from mania-like behavior to depressive-like behavior and vice versa. The use of viral tools and a focus on circadian rhythms and the immune system might make the creation of such animal models possible.

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Section: Resultsmentioning

confidence: 99%

Animal models for bipolar disorder: from bedside to the cage

Beyer

Freund

2017

Int J Bipolar Disord

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“…Alcohol has a number of epigenetic effects on a variety of tissues (Basavarajappa and Subbanna, 2016, Shukla and Lim, 2013) including increased histone deacetylase (HDAC) activity resulting in silencing of gene expression. (Palmisano and Pandey, 2017, Kirpich et al, 2013) For example, alcohol craving is associated with brain H3ac deacetylation with a concurrent increase in brain HDAC expression (Palmisano and Pandey, 2017) that can be reversed with administration of oral sodium butyrate. (Simon-O’Brien et al, 2014, Legastelois et al, 2013) Indeed, in the current study H3ac at the Notch1 locus was deacetylated resulting in Notch1 suppression in alcohol-fed mice as shown by ChiP-PCR (Figure 6D).…”

Section: Discussionmentioning

confidence: 99%

Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate

Forsyth

Shaikh

Bishehsari

et al. 2017

Alcoholism Clin & Exp Res

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Background Alcohol increases intestinal permeability to pro-inflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. Methods Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis/inflammation, and stool short chain fatty acids (SCFA) were measured. Jejunum and colon organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA-seq. ChIP-PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3. Results Alcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colon tissue and organoid staining exhibited an alcohol-induced significant decrease in cytokeratin 20+ (Krt20) absorptive lineage enterocytes, a decrease in occludin and E-cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol-induced decrease in colon organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colon tissue ChIP-PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining. Conclusions Data support a model for alcohol-induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability.

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“…Furthermore, many genes are oppositely regulated by acute ethanol exposure and in ethanol withdrawal. 2 Practically, this suggests that detailed mechanistic understanding of acute ethanol exposure action, especially when coupled to measures of behavioral plasticity, will provide insight into the more complex mechanisms underlying addiction.…”

Section: Introductionmentioning

confidence: 99%

Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance

Adhikari

Orozco

Randhawa

et al. 2018

Genes Brain and Behavior

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Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase is required to terminate Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/β neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.

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Epigenetic mechanisms of alcoholism and stress-related disorders

Cited by 89 publications

References 176 publications

Animal models for bipolar disorder: from bedside to the cage

Animal models for bipolar disorder: from bedside to the cage

Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate

Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance

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