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.

Chronic Alcohol Consumption Increases the Expression of Uncoupling Protein-2 and -4 in the Brain

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Jan A. Graw ◽  
Clarissa von Haefen ◽  
Deniz Poyraz ◽  
Nadine Möbius ◽  
Marco Sifringer ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
The Brain

scholarly journals Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Patrick P. Lowe ◽  
Caroline Morel ◽  
Aditya Ambade ◽  
Arvin Iracheta-Vellve ◽  
Erica Kwiatkowski ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Immune Cell ◽  
Neuronal Damage ◽  
Microglia Activation ◽  
Macrophage Infiltration ◽  
Choice Test ◽  
Chronic Alcohol ◽  
Behavioral Alterations ◽  
Chronic Alcohol Consumption ◽  
The Brain

Abstract Background Chronic alcohol consumption is associated with neuroinflammation, neuronal damage, and behavioral alterations including addiction. Alcohol-induced neuroinflammation is characterized by increased expression of proinflammatory cytokines (including TNFα, IL-1β, and CCL2) and microglial activation. We hypothesized chronic alcohol consumption results in peripheral immune cell infiltration to the CNS. Since chemotaxis through the CCL2-CCR2 signaling axis is critical for macrophage recruitment peripherally and centrally, we further hypothesized that blockade of CCL2 signaling using the dual CCR2/5 inhibitor cenicriviroc (CVC) would prevent alcohol-induced CNS infiltration of peripheral macrophages and alter the neuroinflammatory state in the brain after chronic alcohol consumption. Methods C57BL/6J female mice were fed an isocaloric or 5% (v/v) ethanol Lieber DeCarli diet for 6 weeks. Some mice received daily injections of CVC. Microglia and infiltrating macrophages were characterized and quantified by flow cytometry and visualized using CX3CR1eGFP/+ CCR2RFP/+ reporter mice. The effect of ethanol and CVC treatment on the expression of inflammatory genes was evaluated in various regions of the brain, using a Nanostring nCounter inflammation panel. Microglia activation was analyzed by immunofluorescence. CVC-treated and untreated mice were presented with the two-bottle choice test. Results Chronic alcohol consumption induced microglia activation and peripheral macrophage infiltration in the CNS, particularly in the hippocampus. Treatment with CVC abrogated ethanol-induced recruitment of peripheral macrophages and partially reversed microglia activation. Furthermore, the expression of proinflammatory markers was upregulated by chronic alcohol consumption in various regions of the brain, including the cortex, hippocampus, and cerebellum. Inhibition of CCR2/5 decreased alcohol-mediated expression of inflammatory markers. Finally, microglia function was impaired by chronic alcohol consumption and restored by CVC treatment. CVC treatment did not change the ethanol consumption or preference of mice in the two-bottle choice test. Conclusions Together, our data establish that chronic alcohol consumption promotes the recruitment of peripheral macrophages into the CNS and microglia alterations through the CCR2/5 axis. Therefore, further exploration of the CCR2/5 axis as a modulator of neuroinflammation may offer a potential therapeutic approach for the treatment of alcohol-associated neuroinflammation.

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 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.

Effects of chronic alcohol consumption on the expression of different NR1 splice variants in the brain of AA and ANA lines of rats

1999 ◽  
Vol 72 (2) ◽  
pp. 166-175 ◽  
Author(s):  
Anett Winkler ◽  
Beatrice Mahal ◽  
Kalervo Kiianmaa ◽  
Walter Zieglgänsberger ◽  
Rainer Spanagel
Keyword(s):  
Alcohol Consumption ◽  
Splice Variants ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
The Brain

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.

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