Browsing by Subject "Alcohol abstinence"

Now showing 1 - 4 of 4
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    Disrupted balance between pro-inflammatory lipid mediators and anti-inflammatory specialized pro-resolving mediators is linked to hyperinflammation in patients with alcoholic hepatitis
    (Frontiers Media, 2024-11-21) Li, Wei; Xia, Ying; Yang, Jing; Sanyal, Arun J.; Shah, Vijay H.; Chalasani, Naga P.; Yu, Qigui; Microbiology and Immunology, School of Medicine
    Background: Alcoholic hepatitis (AH) is characterized by intense systemic and liver inflammation, posing significant risks of health complications and mortality. While inflammation is a crucial defense mechanism against injury and infection, its timely resolution is essential to prevent tissue damage and restore tissue homeostasis. The resolution of inflammation is primarily governed by specialized pro-resolving mediators (SPMs), lipid metabolites derived from w-6 and w-3 poly-unsaturated fatty acids (PUFAs). Currently, the balance between pro-inflammatory lipid mediators (PLMs) and SPMs in the w-6 and w-3 PUFA metabolic pathways and the impact of alcohol abstinence on profiles of PLMs and SPMs in AH patients are not well studied. Methods: In this study, we used LC-MS/MS and ELISA to quantify levels of lipid mediators (LMs) and their precursors in the plasma samples from 58 AH patients, 29 heavy drinkers without overt liver diseases (HDCs), and 35 healthy controls (HCs). Subsequently, we assessed correlations of altered LMs with clinical parameters and inflammatory mediators. Furthermore, we conducted a longitudinal study to analyze the effects of alcohol abstinence on LMs over 6- and 12-month follow-ups. Results: AH patients exhibited significantly higher plasma levels of w-6 PLMs (PGD2 and LTB4) and SPM RvE1 compared to HDCs or HCs. Conversely, the SPM LXA4 was significantly downregulated in AH patients. Some of these altered LMs were found to correlate with AH disease severity and various inflammatory cytokines. Particularly, the LTB4/LXA4 ratio was substantially elevated in AH patients relative to HDCs and HCs. This altered ratio displayed a positive correlation with the MELD score. Importantly, the majority of dysregulated LMs, particularly PLMs, were normalized following alcohol abstinence.
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    Species differences in comorbid alcohol use disorder and major depressive disorder: A narrative review
    (Wiley, 2025) Winkler, Garrett A.; Grahame, Nicholas J.; Psychology, School of Science
    Alcohol use disorder (AUD) and major depressive disorder (MDD) are often comorbid, and it is estimated that between 15 % to 33% of people dependent on alcohol have an MDD diagnosis. Mood‐related symptoms are also common in humans during acute withdrawal, but by most accounts, symptoms abate after 2–4 weeks of alcohol abstinence. Preclinical studies, important for understanding the etiology and finding treatments for this comorbidity, also find depression‐like and anxiety‐like phenotypes in early abstinence along with protracted negative affect detectable past 2 weeks postcessation. In this narrative review, we focus on the translational divergence of AUD and MDD comorbidity with a focus on the time line mismatch between species in concurrent AUD + MDD and MDD following AUD. We also highlight the preclinical success and clinical failure of classic antidepressants for AUD and the relative absence of withdrawal and negative affect in high‐drinking selected lines of mice and rats. We suggest sources of these discrepancies, including discussion of relief/reward‐driven drinking subpopulations and future directions for the field.
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    Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol
    (Oxford University Press, 2020-08-14) Hauser, Sheketha R.; Smith, Rebecca J.; Toalston, Jamie E.; Rodd, Zachary A.; McBride, William J.; Bell, Richard L.; Psychiatry, School of Medicine
    Aims: Abstinence after chronic alcohol consumption leads to withdrawal symptoms, which are exacerbated after repeated cycles of relapse. This study examined withdrawal-like behaviors after chronic ethanol drinking, with or without repeated cycles of deprivation. Methods: Male alcohol-preferring (P) rats had access to continuous ethanol (CE), chronic ethanol with repeated deprivation (RD), or remained ethanol naïve (EN). The RD group experienced seven cycles of 2 weeks of deprivation and 2 weeks of re-exposure to ethanol after an initial 6 weeks of ethanol access. Withdrawal was measured after an initial 24 h of ethanol re-exposure in the RD group, which coincided with the same day of ethanol access in the CE group. Withdrawal-like behavior was measured by (a) ethanol intake during the initial 24 h of re-exposure, (b) locomotor activity (LMA) in a novel field 9-13 h after removal of ethanol at the beginning of the fifth re-exposure cycle and (c) acoustic startle responding (ASR) 8-15 h after removal of ethanol at the beginning of the sixth re-exposure cycle. Results: The RD rats displayed a 1-h alcohol deprivation effect (ADE) (temporary ethanol increase), relative to CE rats, during the first to fourth and seventh re-exposure cycles. RD and CE rats displayed significant increases in LMA than EN rats. Regarding ASR, RD rats displayed significantly greater ASR relative to EN rats. Conclusion: This study confirms that P rats meet the animal model criterion for ethanol-associated dependence, without a reliance on either behavioral (limited fluid access) or pharmacological (seizure threshold manipulation) challenges.
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    The impact of abstinence from chronic alcohol consumption on the mouse striatal proteome: sex and subregion-specific differences
    (Frontiers Media, 2024-06-03) Duffus, Brittnie-Lee M.; Haggerty, David L.; Doud, Emma H.; Mosley, Amber L.; Yamamoto, Bryan K.; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    Alcohol misuse is the third leading preventable cause of death in the world. The World Health Organization currently estimates that 1 in 20 deaths are directly alcohol related. One of the ways in which consuming excessive levels of alcohol can both directly and indirectly affect human mortality and morbidity, is through chronic inflammation. Recently, studies have suggested a link between increased alcohol use and the incidence of neuroinflammatory-related diseases. However, the mechanism in which alcohol potentially influences neuroinflammatory processes is still being uncovered. We implemented an unbiased proteomics exploration of alcohol-induced changes in the striatum, with a specific emphasis on proteins related to inflammation. The striatum is a brain region that is critically involved with the progression of alcohol use disorder. Using mass spectrometry following voluntary alcohol self-administration in mice, we show that distinct protein abundances and signaling pathways in different subregions of the striatum are disrupted by chronic exposure to alcohol compared to water drinking control mice. Further, in mice that were allowed to experience abstinence from alcohol compared to mice that were non-abstinent, the overall proteome and signaling pathways showed additional differences, suggesting that the responses evoked by chronic alcohol exposure are dependent on alcohol use history. To our surprise we did not find that chronic alcohol drinking or abstinence altered protein abundance or pathways associated with inflammation, but rather affected proteins and pathways associated with neurodegeneration and metabolic, cellular organization, protein translation, and molecular transport processes. These outcomes suggest that in this drinking model, alcohol-induced neuroinflammation in the striatum is not a primary outcome controlling altered neurobehavioral function, but these changes are rather mediated by altered striatal neuronal structure and cellular health.