scholarly journals Transcriptional Correlates of Chronic Alcohol Neuroadaptation in Drosophila Larvae

2021 ◽  
Vol 15 ◽  
Author(s):  
Amanda Anqueira-González ◽  
Jenny P. Acevedo-Gonzalez ◽  
Airined Montes-Mercado ◽  
Claudia Irizarry-Hernández ◽  
Nicolás L. Fuenzalida-Uribe ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Conditioned Stimulus ◽  
Alcohol Exposure ◽  
Fruit Fly ◽  
Chronic Alcohol ◽  
Larval Brain ◽  
Olfactory Conditioning ◽  
Behavioral Decision ◽  
Cognitive Problems ◽  
Cellular Components

When presented with the choice, Drosophila melanogaster females will often prefer to lay eggs on food containing a significant amount of alcohol. While, in some cases, this behavioral decision can provide a survival advantage to the developing larvae, it can also lead to developmental and cognitive problems. Alcohol consumption can affect executive functions, episodic memory, and other brain function capacities. However, in the fruit fly, the initial cognitive effects of alcohol consumption have been shown to reverse upon persistent exposure to alcohol. Using an olfactory conditioning assay where an odorant is implemented as a conditioned stimulus and paired with a heat shock as an unconditioned stimulus, a previous study has shown that when exposed to a short acute dose of alcohol, Drosophila larvae can no longer learn this association. Interestingly, upon prolonged chronic alcohol exposure, larvae seem to successfully avoid the conditioned stimulus just as well as control alcohol-naive larvae, suggestive of alcohol-induced neuroadaptations. However, the mechanisms by which Drosophila adapt to the presence of alcohol remains unknown. In this study, we explore the transcriptional correlates of neuroadaptation in Drosophila larvae exposed to chronic alcohol to understand the genetic and cellular components responsible for this adaptation. For this, we employed RNA sequencing technology to evaluate differences in gene expression in the brain of larvae chronically exposed to alcohol. Our results suggest that alcohol-induced neuroadaptations are modulated by a diverse array of synaptic genes within the larval brain through a series of epigenetic modulators.

scholarly journals Alcohol induced hepatic retinoid depletion is associated with the induction of multiple retinoid catabolizing cytochrome P450 enzymes

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261675
Author(s):  
Afroza Ferdouse ◽  
Rishi R. Agrawal ◽  
Madeleine A. Gao ◽  
Hongfeng Jiang ◽  
William S. Blaner ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Liver Disease ◽  
Alcohol Consumption ◽  
Vitamin A ◽  
Alcohol Exposure ◽  
Chronic Alcohol ◽  
Wild Type ◽  
Chronic Alcohol Consumption ◽  
Retinyl Esters

Chronic alcohol consumption leads to a spectrum of liver disease that is associated with significant global mortality and morbidity. Alcohol is known to deplete hepatic vitamin A content, which has been linked to the pathogenesis of alcoholic liver disease. It has been suggested that induction of Cytochrome P450 2E1 (CYP2E1) contributes to alcohol-induced hepatic vitamin A depletion, but the possible contributions of other retinoid-catabolizing CYPs have not been well studied. The main objective of this study was to better understand alcohol-induced hepatic vitamin A depletion and test the hypothesis that alcohol-induced depletion of hepatic vitamin A is due to CYP-mediated oxidative catabolism. This hypothesis was tested in a mouse model of chronic alcohol consumption, including wild type and Cyp2e1 -/- mice. Our results show that chronic alcohol consumption is associated with decreased levels of hepatic retinol, retinyl esters, and retinoic acid. Moreover, the depletion of hepatic retinoid is associated with the induction of multiple retinoid catabolizing CYPs, including CYP26A1, and CYP26B1 in alcohol fed wild type mice. In Cyp2e1 -/- mice, alcohol-induced retinol decline is blunted but retinyl esters undergo a change in their acyl composition and decline upon alcohol exposure like WT mice. In conclusion, the alcohol induced decline in hepatic vitamin A content is associated with increased expression of multiple retinoid-catabolizing CYPs, including the retinoic acid specific hydroxylases CYP26A1 and CYP26B1.

scholarly journals The effect of chronic alcohol consumption on mitochondrial calcium handling in hepatocytes

2016 ◽  
Vol 473 (21) ◽  
pp. 3903-3921 ◽  
Author(s):  
Guoqiang Wang ◽  
Elisabeth Mémin ◽  
Ishwarya Murali ◽  
Lawrence D. Gaspers
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Exposure ◽  
Liver Mitochondria ◽  
Calcium Handling ◽  
Chronic Alcohol ◽  
Transport Pathway ◽  
Excessive Alcohol Consumption ◽  
Intact Cells ◽  
Mitochondrial Ros ◽  
Excessive Alcohol

The damage to liver mitochondria is universally observed in both humans and animal models after excessive alcohol consumption. Acute alcohol treatment has been shown to stimulate calcium (Ca2+) release from internal stores in hepatocytes. The resultant increase in cytosolic Ca2+ is expected to be accumulated by neighboring mitochondria, which could potentially lead to mitochondrial Ca2+ overload and injury. Our data indicate that total and free mitochondrial matrix Ca2+ levels are, indeed, elevated in hepatocytes isolated from alcohol-fed rats compared with their pair-fed control littermates. In permeabilized hepatocytes, the rates of mitochondrial Ca2+ uptake were substantially increased after chronic alcohol feeding, whereas those of mitochondrial Ca2+ efflux were decreased. The changes in mitochondrial Ca2+ handling could be explained by an up-regulation of the mitochondrial Ca2+ uniporter and loss of a cyclosporin A-sensitive Ca2+ transport pathway. In intact cells, hormone-induced increases in mitochondrial Ca2+ declined at slower rates leading to more prolonged elevations of matrix Ca2+ in the alcohol-fed group compared with controls. Moreover, treatment with submaximal concentrations of Ca2+-mobilizing hormones markedly increased the levels of mitochondrial reactive oxygen species (ROS) in hepatocytes from alcohol-fed rats, but did not affect ROS levels in controls. The changes in mitochondrial Ca2+ handling are expected to buffer and attenuate cytosolic Ca2+ increases induced by acute alcohol exposure or hormone stimulation. However, these alterations in mitochondrial Ca2+ handling may also lead to Ca2+ overload during cytosolic Ca2+ increases, which may stimulate the production of mitochondrial ROS, and thus contribute to alcohol-induced liver injury.

scholarly journals Transcriptome Analysis of Alcohol Drinking in Non-Dependent and Dependent Mice Following Repeated Cycles of Forced Swim Stress Exposure

2020 ◽  
Vol 10 (5) ◽  
pp. 275
Author(s):  
Sean P. Farris ◽  
Gayatri R. Tiwari ◽  
Olga Ponomareva ◽  
Marcelo F. Lopez ◽  
R. Dayne Mayfield ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Exposure ◽  
Maladaptive Behavior ◽  
Chronic Alcohol ◽  
Swim Stress ◽  
Forced Swim ◽  
Chronic Intermittent Ethanol ◽  
Forced Swim Stress ◽  
Chronic Alcohol Exposure ◽  
Regulated Gene Expression

Chronic stress is a known contributing factor to the development of drug and alcohol addiction. Animal models have previously shown that repeated forced swim stress promotes escalated alcohol consumption in dependent animals. To investigate the underlying molecular adaptations associated with stress and chronic alcohol exposure, RNA-sequencing and bioinformatics analyses were conducted on the prefrontal cortex (CTX) of male C57BL/6J mice that were behaviorally tested for either non-dependent alcohol consumption (CTL), chronic intermittent ethanol (CIE) vapor dependent alcohol consumption, repeated bouts of forced swim stress alone (FSS), and chronic intermittent ethanol with forced swim stress (CIE + FSS). Brain tissue from each group was collected at 0-h, 72-h, and 168-h following the final test to determine long-lasting molecular changes associated with maladaptive behavior. Our results demonstrate unique temporal patterns and persistent changes in coordinately regulated gene expression systems with respect to the tested behavioral group. For example, increased expression of genes involved in “transmitter-gated ion channel activity” was only determined for CIE + FSS. Overall, our results provide a summary of transcriptomic adaptations across time within the CTX that are relevant to understanding the neurobiology of chronic alcohol exposure and stress.

Chronic Alcohol Exposure Alters Gene Expression and Neurodegeneration Pathways in the Brain of Adult Mice

2022 ◽  
pp. 1-17
Author(s):  
Mingjing Liu ◽  
Shipeng Guo ◽  
Daochao Huang ◽  
Dongjie Hu ◽  
Yili Wu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Alcohol Consumption ◽  
Alcohol Exposure ◽  
Chronic Alcohol ◽  
Rna Seq ◽  
Chronic Alcohol Consumption ◽  
Mitochondrial Energy Metabolism ◽  
Brain Transcriptome ◽  
Chronic Alcohol Exposure ◽  
The Brain

Background: Chronic alcohol consumption can alter the structure of the central nervous system and disrupt cognitive function. Alcoholics are more likely to develop neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the role of alcohol in promoting neurotoxicity and neurodegeneration remains unclear. Objective: In this study, we aimed at estimating the effects of chronic binge alcohol exposure on brain transcriptome and behavior changes in a chronic “Drinking in the Dark” (DID) mouse model. Methods: The adult C57BL/6J male mice were exposed to alcohol for 4 weeks. RNA-seq was applied to assess the effects of chronic alcohol exposure on transcriptome in brain. The open field test and novel object recognition test were used to assess the changes of anxiety level, locomotive function, and short-term memory induced by alcohol. RNA-seq analysis revealed that chronic alcohol exposure caused significant change in the brain transcriptome, especially in prefrontal cortex. Results: The gene dysregulation caused by chronic alcohol exposure includes pathways related to mitochondrial energy metabolism (such as oxidative phosphorylation) and multiple neurodegenerative diseases (such as AD and PD). Furthermore, the pathway and network analyses suggest that the genes involved in mitochondrial energy metabolism, ubiquitin-proteasome system, Wnt signaling pathway, and microtubules may attribute to the neurotoxicity and neurodegeneration caused by chronic alcohol consumption. Additionally, locomotive function was also significantly impaired. Conclusion: This work provides gene transcriptional profile data for future research on alcohol-induced neurodegenerative diseases, especially AD and PD.

scholarly journals Biomarker Signatures to Monitor Alcohol Consumption and Induced Organ Damage

2021 ◽  
Author(s):  
Joy M Liji ◽  
PR Varghese ◽  
Susheela Jacobinnah ◽  
Praveenlal Kuttichira
Keyword(s):  
Sialic Acid ◽  
Alcohol Consumption ◽  
English Language ◽  
Alcohol Exposure ◽  
Organ Damage ◽  
Ethyl Esters ◽  
Total Serum ◽  
Free Access ◽  
Chronic Alcohol ◽  
Keywords Alcohol

The difficulty to differentiate long duration alcoholic behaviours is a major obstacle in the diagnosis and its treatment. Biomarkers in alcoholism are indicative of recent alcohol consumption or alcohol-induced organ damage. They are broadly divided into two; state markers, which are tools indicative of acute or chronic alcohol consumption, and trait markers, which are markers indicative of a genetic predisposition responsible to develop alcohol dependence. This review aimed to sensitise the practitioners on different alcohol state markers available now-a-days. An electronic search in Google Scholar, MEDLINE, and PubMed was conducted by using following keywords: Alcohol biomarkers, State markers, Trait markers, Alcohol consumption test. Studies on alcohol biomarkers published in English language were included in this review. Reviews and studies with free access to only abstract have been excluded. The state markers mostly used to identify chronic alcohol exposure are the Gamma-Glutamyltransferase (GGT), Aspartate and Alanine Aminotransferase (AST and ALT) which are routine serum liver function panels and Mean Corpuscular Volume (MCV) which is a haematological marker. The available non-conventional state biomarkers are Phosphatidylethanol (PEth), Fatty Acid Ethyl Esters (FAEE) and 5-Hydroxytryptophol (5-HTOL). The novel state markers which have been developed in recent research context are still awaiting validation and possible introduction to commercial settings are Plasma Sialic Acid Index of Apolipoprotein J (SIJ), Total Serum Sialic Acid (TSA), Acetaldehyde, Acetaldehyde adducts, anti-adduct antibodies and β-Hexosaminidase. Conventional alcohol biomarkers are routinely used in clinical practice. Non-conventional biomarkers seem to be promising for its estimation. Novel biomarkers are at various stages of research and development.

scholarly journals A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2177
Author(s):  
Zhipeng Cao ◽  
Tianqi Wang ◽  
Wei Xia ◽  
Baoli Zhu ◽  
Meihui Tian ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Left Ventricle ◽  
Cardiac Function ◽  
Myocardial Injury ◽  
Alcohol Exposure ◽  
Differentially Expressed ◽  
Chronic Alcohol ◽  
Metabolomic Analysis ◽  
Alcoholic Cardiomyopathy ◽  
Chronic Alcohol Consumption

Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson’s trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.

scholarly journals Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Hsiang Lin ◽  
Oswald Ndi Nfor ◽  
Chien-Chang Ho ◽  
Shu-Yi Hsu ◽  
Disline Manli Tantoh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Alcohol Consumption ◽  
Genetic Variants ◽  
Regression Models ◽  
Hemorrhagic Stroke ◽  
Alcohol Exposure ◽  
Modifiable Risk Factors ◽  
Aldehyde Dehydrogenase 2 ◽  
Logistic Regression Models ◽  
Increased Risk

Abstract Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean  ±  SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p  <  0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC  +  CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92–12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction  =  0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC  +  CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19–16.52). Conclusions Our study suggests that the ADH1B rs1229984 TC  +  CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

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