Emerging Role of Epigenetic Mechanisms in Alcohol Addiction

Berkel, Tiffani D.M.; Pandey, Subhash C.

doi:10.1111/acer.13338

Cited by 93 publications

(79 citation statements)

References 172 publications

(257 reference statements)

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“…It is possible that binge alcohol changed the expression levels of trophic factors in the brain, for instance, BDNF, GDNF, and EGF are all important for neurogenesis and are affected by alcohol (Janak et al, ). Additionally, it is possible that alcohol is affecting neurogenesis via epigenetic mechanisms (see Berkel & Pandey, for review). One study found reduced methylation of the CpG (Cytosin‐phosphatidyl‐Guanin) of the promoter of NGF in the serum of alcohol dependent patients (Heberlein et al, ).…”

Section: Discussionmentioning

confidence: 99%

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Ton

Tsai

Vaagenes

et al. 2019

J of Neuroscience Research

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Traumatic brain injury (TBI) is a major cause of disability worldwide. Additionally, many TBI patients are intoxicated with alcohol at the time of injury, but the impact of acute intoxication on recovery from brain injury is not well understood. We have previously found that binge alcohol prior to TBI impairs spontaneous functional sensorimotor recovery. However, whether alcohol administration in this setting affects reactive neurogenesis after TBI is not known. This study therefore sought to determine the short and long term effects of pre-TBI binge alcohol on neural precursor cell responses in the subventricular zone (SVZ) following brain injury in male rats. We found that TBI alone significantly increased proliferation in the SVZ as early as 24 hours after injury. Surprisingly, binge alcohol alone also significantly increased proliferation in the SVZ after 24 hours. However, a combined binge alcohol and TBI regimen resulted in decreased TBI-induced proliferation in the SVZ at 24 hours and 1 week post-TBI. Furthermore, at 6 weeks after TBI, binge alcohol administered at the time of TBI significantly decreased the TBI-induced neuroblast response in the SVZ and the rostral migratory stream (RMS). The results from this study suggest that pre-TBI binge alcohol negatively impacts reparative processes in the brain by decreasing short-term neural precursor cell proliferative responses as well as long-term neuroblasts in the SVZ and RMS.

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Section: Discussionmentioning

confidence: 99%

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Ton

Tsai

Vaagenes

et al. 2019

J of Neuroscience Research

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“…Interestingly, genome-wide association studies (GWAS) have identified the genomic region encompassing the histone demethylase KDM4C gene as a hotspot associated with alcohol withdrawal symptoms (Wang et al, 2012). As research into the negative affective states seen during alcohol withdrawal and addiction continues, additional epigenetic modifications such as histone methylation, phosphorylation, and others may emerge as novel biomarkers of alcohol-induced anxiety in brain circuits such as the amygdala (Krishnan et al, 2014; Berkel and Pandey, 2017). …”

Section: Chronic Alcohol Exposure-induced Withdrawal Is Anxiogenicmentioning

confidence: 99%

Epigenetic basis of the dark side of alcohol addiction

2017

Self Cite

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Alcoholism is a complex brain disease characterized by three distinct stages of the addiction cycle that manifest as neuroadaptive changes in the brain. One such stage of the addiction cycle is alcohol withdrawal and the negative affective states that promote drinking and maintain addiction. Repeated alcohol use, genetic predisposition to alcoholism and anxiety, and alcohol exposure during crucial developmental periods all contribute to the development of alcohol-induced withdrawal and negative affective symptoms. Epigenetic modifications within the amygdala have provided a molecular basis of these negative affective symptoms, also known as the dark side of addiction. Here, we propose that allostatic change within the epigenome in the amygdala is a prime mechanism of the biological basis of negative affective states resulting from, and contributing to, alcoholism. Acute alcohol exposure produces an anxiolytic response which is associated with the opening of chromatin due to increased histone acetylation, increased CREB binding protein (CBP) levels, and histone deacetylase (HDAC) inhibition. After chronic ethanol exposure, these changes return to baseline along with anxiety-like behaviors. However, during withdrawal, histone acetylation decreases due to increased HDAC activity and decreased CBP levels in the amygdala circuitry leading to the development of anxiety-like behaviors. Additionally, innately higher expression of the HDAC2 isoform leads to a deficit in global and gene-specific histone acetylation in the amygdala that is associated with a decrease in the expression of several synaptic plasticity-associated genes and maintaining heightened anxiety-like behavior and excessive alcohol intake. Adolescent alcohol exposure also leads to higher expression of HDAC2 and a deficit in histone acetylation leading to decreased expression of synaptic plasticity-associated genes and high anxiety and drinking behavior in adulthood. All these studies indicate that the epigenome can undergo allostatic reprogramming in the amygdaloid circuitry during various stages of alcohol exposure. Furthermore, opening the chromatin by inhibiting HDACs using pharmacological or genetic manipulations can lead to the attenuation of anxiety as well as alcohol intake. Chromatin remodeling provides a clear biological basis for the negative affective states seen during alcohol addiction and presents opportunities for novel drug development and treatment options.

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“…As many of the associated articles have reported, acute, chronic and intermittent exposures to alcohol have substantial epigenetic effects (see e.g. Berkel and Pandey 2017; Lopez-Moreno et al 2015). While the breadth of epigenetic changes in synaptic function remain to be completely determined, changes in genes e.g.…”

Section: Discussionmentioning

confidence: 99%

Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)

Hitzemann

Oberbeck

Iancu

et al. 2017

Alcohol

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Among animals at risk for excessive ethanol consumption such as the HDID selected lines, there is considerable individual variation in the amount of ethanol consumed and the associated blood ethanol concentrations (BECs). For the HDID lines, this variation occurs even though the residual genetic variation associated with the DID phenotype has been largely exhausted and thus is most likely associated with epigenetic factors. Here we focus on the question of whether the genes associated with individual variation in HDID-1 mice are different from those associated with selection (risk) ( Iancu et al. 2013). Thirty-three HDID-1 mice were phenotyped for their BECs at the end of a standard DID trial, were sacrificed 3 weeks later and RNA-Seq was used to analyze the striatal transcriptome. The data obtained illustrated that there is considerable overlap of the risk and variation gene sets; both focus on the fine tuning of synaptic plasticity.

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Emerging Role of Epigenetic Mechanisms in Alcohol Addiction

Cited by 93 publications

References 172 publications

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Epigenetic basis of the dark side of alcohol addiction

Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)

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