scholarly journals Proteomics reveals profound metabolic changes in the alcohol use disorder brain

2018 ◽  
Author(s):  
Charmaine Enculescu ◽  
Edward D. Kerr ◽  
K. Y. Benjamin Yeo ◽  
Peter R. Dodd ◽  
Gerhard Schenk ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Substantial Effect ◽  
Biochemical Processes ◽  
Data Independent Acquisition ◽  
Metabolic Adaptations ◽  
Brain Proteome ◽  
Acetate Utilization ◽  
The Brain

AbstractChanges in brain metabolism are a hallmark of Alcohol Use Disorder (AUD). Determining how AUD changes the brain proteome is critical for understanding the effects of alcohol consumption on biochemical processes in the brain. We used data-independent acquisition mass spectrometry proteomics to study differences in the abundance of proteins associated with AUD in pre-frontal lobe and motor cortex from autopsy brain. AUD had a substantial effect on the overall brain proteome exceeding the inherent differences between brain regions. Proteins associated with glycolysis, trafficking, the cytoskeleton, and excitotoxicity were altered in abundance in AUD. We observed extensive changes in the abundance of key metabolic enzymes, consistent with a switch from glucose to acetate utilization in the AUD brain. We propose that metabolic adaptations allowing efficient acetate utilization contribute to ethanol dependence in AUD.

Animal models of alcohol use disorder and the brain: From casual drinking to dependence.

2019 ◽  
Vol 5 (3) ◽  
pp. 222-242 ◽  
Author(s):  
Nicole A. Crowley ◽  
Nigel C. Dao ◽  
Sarah N. Magee ◽  
Alexandre J. Bourcier ◽  
Emily G. Lowery-Gionta
Keyword(s):  
Alcohol Use ◽  
Animal Models ◽  
Alcohol Use Disorder ◽  
The Brain

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

scholarly journals Alcohol use disorder causes global changes in splicing in the human brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Derek Van Booven ◽  
Mengying Li ◽  
J. Sunil Rao ◽  
Ilya O. Blokhin ◽  
R. Dayne Mayfield ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Human Brain ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Gene Set Enrichment Analysis ◽  
Splicing Factor ◽  
Central Nucleus ◽  
Global Changes ◽  
Aberrant Expression ◽  
Altered Expression

AbstractAlcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

scholarly journals Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder

2020 ◽  
Vol 6 (1) ◽  
pp. 47-66 ◽  
Author(s):  
Ignatius Alvarez Cooper ◽  
Kate Beecher ◽  
Fatemeh Chehrehasa ◽  
Arnauld Belmer ◽  
Selena E. Bartlett
Keyword(s):  
Alcohol Use ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Alcohol Use Disorder ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Neuroimmune System ◽  
Inflammatory Status ◽  
The Brain ◽  
Necrosis Factor

Alcohol use disorder is a pervasive and detrimental condition that involves changes in neuroplasticity and neurogenesis. Alcohol activates the neuroimmune system and alters the inflammatory status of the brain. Tumour necrosis factor (TNF) is a well characterised neuroimmune signal but its involvement in alcohol use disorder is unknown. In this review, we discuss the variable findings of TNF’s effect on neuroplasticity and neurogenesis. Acute ethanol exposure reduces TNF release while chronic alcohol intake generally increases TNF levels. Evidence suggests TNF potentiates excitatory transmission, promotes anxiety during alcohol withdrawal and is involved in drug use in rodents. An association between craving for alcohol and TNF is apparent during withdrawal in humans. While anti-inflammatory therapies show efficacy in reversing neurogenic deficit after alcohol exposure, there is no evidence for TNF’s essential involvement in alcohol’s effect on neurogenesis. Overall, defining TNF’s role in alcohol use disorder is complicated by poor understanding of its variable effects on synaptic transmission and neurogenesis. While TNF may be of relevance during withdrawal, the neuroimmune system likely acts through a larger group of inflammatory cytokines to alter neuroplasticity and neurogenesis. Understanding the individual relevance of TNF in alcohol use disorder awaits a more comprehensive understanding of TNF’s effects within the brain.

scholarly journals Family history of alcohol use disorder is associated with brain structural and functional changes in healthy first-degree relatives

2019 ◽  
Vol 62 ◽  
pp. 107-115 ◽  
Author(s):  
Irina Filippi ◽  
Nicolas Hoertel ◽  
Eric Artiges ◽  
Guillaume Airagnes ◽  
Christophe Guérin-Langlois ◽  
...  
Keyword(s):  
Family History ◽  
Alcohol Use ◽  
Childhood Maltreatment ◽  
Alcohol Use Disorder ◽  
Grey Matter ◽  
Brain Regions ◽  
Whole Brain ◽  
Childhood Trauma Questionnaire ◽  
Functional Changes ◽  
History Of

Abstract Background: Neuroimaging studies of vulnerability to Alcohol Use Disorder (AUD) have identified structural and functional variations which might reflect inheritable features in alcohol-naïve relatives of AUD individuals (FH+) compared to controls having no such family history (FH-). However, prior research did not simultaneously account for childhood maltreatment, any clinically significant disorder and maternal AUD. Therefore, we mainly aimed to investigate the brain structure and reward-related neural activations (fMRI), using whole-brain analysis in FH+ young adults with no prevalent confounders. Methods: 46 FH+ and 45 FH- male and female participants had no severe childhood maltreatment exposure, neither any psychiatric disorder or AUD, nor a prenatal exposure to maternal AUD. We used a 3 T MRI coupled with a whole brain voxel-based method to compare between groups the grey matter volumes and activations in response to big versus small wins during a Monetary Incentive Delay task. The Childhood Trauma Questionnaire score was used as confounding variable in the analyses to account for the remaining variance between groups. Results: Compared to FH- controls, FH+ participants had smaller grey matter volumes in the frontal and cingulate regions as well as in the bilateral nucleus accumbens and right insula. The FH+ participants’ fMRI datasets denoted a blunted activation in the middle cingulum with respect to FH- controls’ during the processing of reward magnitude, and a greater activation in the anterior cingulum in response to anticipation of a small win. Conclusions: Family history of alcohol use disorder is linked to structural and functional variations including brain regions involved in reward processes.

scholarly journals Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain

2019 ◽  
Vol 10 ◽  
Author(s):  
Julia De Ternay ◽  
Mickaël Naassila ◽  
Mikail Nourredine ◽  
Alexandre Louvet ◽  
François Bailly ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
The Brain

Motor Timing as a Predictor of Attention, Working Memory and Impulsivity in Alcohol and/or Cocaine Use Disorders

2020 ◽  
pp. 1-25
Author(s):  
S.Y. Young ◽  
J.J.M. van Hoof ◽  
M. Kidd ◽  
S. Seedat
Keyword(s):  
Working Memory ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Motor Timing ◽  
Motor Tasks ◽  
Cognitive Demands ◽  
Cocaine Use ◽  
Neurotoxic Effects ◽  
Millisecond Timing ◽  
The Brain

In recent years, there has been a growing interest in neuropsychological deficits in patients with Cocaine Use Disorder (CUD) and Alcohol Use Disorder (AUD). Besides deficits in working memory (WM), impulsivity and attention, chronic alcohol and cocaine use have neurotoxic effects on frontostriatal areas in the brain. Individuals with deficits in these brain regions experience motor-timing deficits. It is unclear whether observed temporal processing deficits, in fact, reflect increased sustained attention or WM demands (which are required by timing tasks), or whether motor-timing deficits reflect some other process. The main questions of this were: (i) Can attention and WM be explained by motor-timing performance, and (ii), is impulsivity related to motor timing performance, in an inpatient SUD population? The study sample consisted of 74 abstinent patients who completed selected neuropsychological and motor-timing tasks. No significant correlation was found between performance on motor tasks and impulsivity. With regard to visual and auditory WM, motor timing was a significant predictor but only under conditions that required increased cognitive demands. Motor-timing performance contributed to a small portion of the variance in attention, but only for spatial abilities and only at increased cognitive demands. These preliminary findings suggest that, in line with the literature, millisecond timing engages other cognitive functions, but only minimally. As such motor timing should be regarded as a separate neurocognitive concomitant. Impulsivity was not associated with millisecond motor timing. More research is needed to further investigate these preliminary findings.

scholarly journals Epigenome-wide Association Study of Alcohol Use Disorder in Five Brain Regions

2021 ◽  
Author(s):  
Lea Zillich ◽  
Josef Frank ◽  
Fabian Streit ◽  
Marion M Friske ◽  
Jerome C Foo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Use ◽  
Brain Region ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Human Brain Tissue ◽  
Postmortem Human Brain ◽  
Association Analyses ◽  
Cpg Sites

Alcohol Use Disorder (AUD) is closely linked to the brain regions forming the neurocircuitry of addiction. Postmortem human brain tissue enables the direct study of the molecular pathomechanisms of AUD. This study aims to identify these mechanisms by examining differential DNA-methylation between cases with severe AUD (n=53) and controls (n=58) using a brain region-specific approach. Samples of the anterior cingulate cortex (ACC), Brodmann Area 9 (BA9), caudate nucleus (CN), ventral striatum (VS), and putamen (PUT) were investigated. DNA-methylation levels were determined using the Illumina HumanMethylationEPIC Beadchip. Epigenome-wide association analyses were carried out to identify differentially methylated CpG-sites and regions between cases and controls in each brain region. Weighted Correlation Network Analysis (WGCNA), gene-set and GWAS-enrichment analyses were performed. Two differentially methylated CpG-sites were associated with AUD in the CN, and 18 in VS (q < .05). No epigenome-wide significant CpG-sites were found in BA9, ACC, or PUT. Differentially methylated regions associated with AUD case-/control status (q < .05) were found in the CN (n=6), VS (n=18) and ACC (n=1). These findings were mapped to several genes including IREB2, SLC30A8, and DDAH2. In the VS, the WGCNA-module showing the strongest association with AUD was enriched for immune-related pathways. This study is the first to analyze methylation differences between AUD cases and controls in multiple brain regions and consists of the largest sample to date. Several novel CpG-sites and regions implicated in AUD were identified, providing a first basis to explore epigenetic correlates of AUD

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