Alcohol (Hanover, York County, Pa.)最新文献

{"title":"The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels","authors":"Aishwarya Thakurdesai,&nbsp;Suman K. Jha,&nbsp;Iyabo Erinkitola,&nbsp;Aula Said,&nbsp;Thwisha Joshi,&nbsp;Melanie L. Schwandt,&nbsp;Dipendra Parajuli,&nbsp;Ashwani K. Singal,&nbsp;Maiying Kong,&nbsp;Matthew C. Cave,&nbsp;Vatsalya Vatsalya","doi":"10.1111/acer.15408","DOIUrl":"10.1111/acer.15408","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-nine male and female AUD patients were grouped by normal [≥71 <i>μ</i>g/dL (Group 1, number (<i>n</i>) = 26)] and low [&lt;71 <i>μ</i>g/dL (Group 2, <i>n</i> = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Group 2 females exhibited lower LTDH than Group 2 males (<i>p</i> = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (<i>p</i> = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (<i>p</i> = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (<i>R</i>² = 0.633, <i>p</i> = 0.037).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1740-1752"},"PeriodicalIF":3.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement","authors":"Valerie Vierkant,&nbsp;Xueyi Xie,&nbsp;Zhenbo Huang,&nbsp;Lian He,&nbsp;Eric Bancroft,&nbsp;Xuehua Wang,&nbsp;Tran Nguyen,&nbsp;Rahul Srinivasan,&nbsp;Yubin Zhou,&nbsp;Jun Wang","doi":"10.1111/acer.15412","DOIUrl":"10.1111/acer.15412","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self-administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1728-1739"},"PeriodicalIF":3.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review of patient contribution to the development of alcohol craving measurements","authors":"Lionel Zeganadin,&nbsp;Jorge Lopez-Castroman,&nbsp;Marc Auriacombe,&nbsp;Amandine Luquiens","doi":"10.1111/acer.15409","DOIUrl":"10.1111/acer.15409","url":null,"abstract":"<p>Craving is considered one of the defining characteristics for alcohol or substance use disorders. There is no consensus on the underlying processes of craving, although multiple models exist. Craving is a very individualistic symptom and has to be self-reported. Several instruments have been developed to measure craving, without a recognized gold standard. The patient's perspective appears critical to determine the relevance of the numerous existing tools. We assessed the contribution of patients to the development of these instruments. We performed a systematic review of instruments measuring alcohol craving published from 2012 to 2023 from three databases (PubMed, PsycInfo, and Embase) in addition to those identified in a previous review by Kavanagh et al. from 1990 to 2012. We included all articles related to the development or validation of instruments for the assessment of alcohol craving. We identified and included in this review the corresponding instruments. Articles translating existing instruments without validation or on single-item instruments were excluded. We analyzed the articles in accordance with COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) recommendations to assess patient involvement in the creation of patient-reported outcome measures (PROM). Two key aspects were investigated: (1) the general design, encompassing the quality of construct description, identification of elements pertinent to a PROM, particularly the inclusion of concepts provided by patients, and (2) the quality of cognitive interviews (when conducted), to evaluate the comprehensiveness and comprehensibility of the PROM. We included 22 articles identifying 16 instruments for measuring alcohol craving. Patients only contributed to item development for one instrument and its short version (QAU and AUQ). None of the instruments met all of the developmental quality criteria, with 14 classed as “inadequate” and two as “doubtful.” The current instruments measuring alcohol craving were developed with poor patient contribution, although most articles did not adequately report patient involvement. Patients' perspectives on craving should be explored for future patient-centered approach.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1637-1656"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The international prevalence of prenatal alcohol use obtained via meconium biomarkers: A systematic literature review","authors":"Orlagh Keating,&nbsp;Ruth H. Brown,&nbsp;Renate Kuenssberg,&nbsp;Sarah Driscoll,&nbsp;Stewart McDougall,&nbsp;Suzanne O'Rourke","doi":"10.1111/acer.15410","DOIUrl":"10.1111/acer.15410","url":null,"abstract":"<p>Fetal alcohol exposure is a growing public health concern. However, ascertaining its true extent remains challenging as maternal self-reports may lack validity. Increasingly, interest has turned to more objective measures of prenatal alcohol use (PAU) of which one, meconium, is recognized as a valuable tool. This review assesses both the international prevalence of PAU obtained using meconium biomarkers in general maternity populations and, when feasible, the level of agreement between meconium biomarkers and self-reported PAU. A systematic literature search for studies reporting the prevalence of PAU, as determined by meconium biomarker testing, was conducted using multiple electronic databases from 1990 to 2023. Seventeen studies were identified for inclusion and evaluated for methodological quality. Using fatty acid ethyl esters (FAEEs) meconium biomarkers, PAU prevalence varied from 2.4% to 44%. Rates based on EtG (ethyl glucuronide) analysis ranged from 0% to 16.3%, and EtS (ethyl sulfate) analysis from 7.8% to 16.7%. Studies were of moderate quality with high heterogeneity. Prevalence rates based on self-report data ranged from 0% to 46.4%. When reported, none of the reviewed studies identified agreement between meconium-based and self-report-based PAU prevalence rates. Using both self-reports to detect early pregnancy alcohol use, and meconium biomarkers to detect the occurrence of alcohol use later in pregnancy, may provide a more complete picture of PAU prevalence. Furthermore, research is warranted to develop stringent guidance on the ascertainment, storage, analysis, and reporting required in this field.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1657-1676"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of adolescent intermittent ethanol exposure on cortical perineuronal net and parvalbumin expression in adulthood mediate behavioral inflexibility","authors":"Emily D. K. Sullivan,&nbsp;Carol A. Dannenhoffer,&nbsp;Elizabeth B. Sutherland,&nbsp;Elena M. Vidrascu,&nbsp;Alexander Gómez-A,&nbsp;Charlotte A. Boettiger,&nbsp;Donita L. Robinson","doi":"10.1111/acer.15395","DOIUrl":"10.1111/acer.15395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads to increased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part <i>through</i> changes in PV and PNN fluorescent measures in the AIC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1507-1518"},"PeriodicalIF":3.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of text-only versus large text-and-picture alcohol warning formats: A functional magnetic resonance imaging study in French young male drinkers","authors":"Karine Gallopel-Morvan,&nbsp;Quentin Duche,&nbsp;Jacques François Diouf,&nbsp;Sophie Lacoste-Badie,&nbsp;Olivier Droulers,&nbsp;Romain Moirand,&nbsp;Elise Bannier","doi":"10.1111/acer.15389","DOIUrl":"10.1111/acer.15389","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Although the World Health Organization recommends visible and clear warning labels about the risks of alcohol consumption on containers and advertising, many of the currently used labels are too small to be visible. This study investigated the brain activity (using fMRI) and alcohol consumption intentions of French young men exposed to two warning formats displayed on alcoholic beverage advertisements: a small Text-only Alcohol Warning (TAW) currently used in many countries, and a larger text-and-picture alcohol warning (PAW).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Seventy-four eligible 18–25-year-old male drinkers completed a face-to-face individual visit with a physician expert in addiction medicine. This was followed by the fMRI session during which they viewed 288 stimuli [96 alcohol advertisements with TAWs, the same 96 advertisements with PAWs, and 96 water advertisements (controls)] for 3 s each. If the advertisement made participants want (“yes”)/do not want (“no”) to consume the product, they pressed the corresponding button (self-report responses). The number of “yes” responses was compared between advertisement types with a paired sample &lt;i&gt;t&lt;/i&gt;-test. Whole-brain and region-of-interest (ROI) analyses of the fMRI data were performed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Whole-brain BOLD fMRI highlighted contrasting effects of PAWs and TAWs. Compared with TAWs, PAWs elicited more activation in the precuneus, angular gyrus, occipital, frontal and temporal areas, and less activation in the nucleus accumbens, ventral tegmental areas, and putamen areas (regions of the reward circuit). The ROI analysis confirmed less activation in the reward circuit (left and right ventral tegmental areas, left and right nucleus accumbens) when viewing PAWs than TAWs. Analysis of the self-report responses indicated that the desire to consume the advertised alcohol product was lower when PAWs were viewed (compared with TAWs) (&lt;i&gt;T&lt;/i&gt; = 8.18, &lt;i&gt;p&lt;/i&gt; &lt; 10&lt;sup&gt;−11&lt;/sup&gt;).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This is the first fMRI study to assess the effect of different alcohol warning formats. Our findings show that compared with TAWs, stronger PAWs in advertisements elicited less activity in key regions of the reward system. This suggests that the effects may influence the desire to consume alcohol products (self-report response analysis). These results could help policymakers who are interested in developing more effective labeling measures that target young people.&lt;/p&gt;\u0000 &lt;/","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1610-1620"},"PeriodicalIF":3.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressants and alcohol use disorder: A multicenter study on the mediating role of depression symptom changes","authors":"Joshua Jaeger,&nbsp;Lara Osterburg,&nbsp;Maria Stein,&nbsp;Miranda Germann,&nbsp;Sara A. Lustenberger,&nbsp;Alexander Wopfner,&nbsp;Niklaus Denier,&nbsp;Tobias Bracht,&nbsp;Franz Moggi,&nbsp;Leila M. Soravia","doi":"10.1111/acer.15386","DOIUrl":"10.1111/acer.15386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co-occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 153 detoxified AUD patients who attended a 12-week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi-Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of days abstinent to assess the role of changes in depression symptoms as a mediating factor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (<i>p</i> = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (<i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1577-1585"},"PeriodicalIF":3.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurosteroid [3α,5α]3-hydroxypregnan-20-one inhibition of chemokine monocyte chemoattractant protein-1 in alcohol-preferring rat brain neurons, microglia, and astroglia","authors":"Samantha Lucenell Chéry,&nbsp;Todd K. O'Buckley,&nbsp;Giorgia Boero,&nbsp;Irina Balan,&nbsp;A. Leslie Morrow","doi":"10.1111/acer.15404","DOIUrl":"10.1111/acer.15404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroimmune dysfunction in alcohol use disorder (AUD) is associated with activation of myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptors (TLR) resulting in overexpression of the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). MCP-1 overexpression in the brain is linked to anxiety, higher alcohol intake, neuronal death, and activation of microglia observed in AUD. The neurosteroid [3α,5α][3-hydroxypregnan-20-one (3α,5α-THP) has been reported as an inhibitor of MyD88-dependent TLR activation and MCP-1 overexpression in mouse and human macrophages and the brain of alcohol-preferring (P) rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated how 3α,5α-THP regulates MCP-1 expression at the cellular level in P rat nucleus accumbens (NAc) and central amygdala (CeA). We focused on neurons, microglia, and astrocytes, examining the individual voxel density of MCP-1, neuronal marker NeuN, microglial marker IBA1, astrocytic marker GFAP, and their shared voxel density, defined as intersection. Ethanol-naïve male and female P rats were perfused 1 h after IP injections of 15 mg/kg of 3α,5α-THP, or vehicle. The NAc and CeA were imaged using confocal microscopy following double-immunofluorescence staining for MCP-1 with NeuN, IBA1, and GFAP, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MCP-1 intersected with NeuN predominantly and IBA1/GFAP negligibly. 3α,5α-THP reduced MCP-1 expression in NeuN-labeled cells by 38.27 ± 28.09% in male and 56.11 ± 21.46% in female NAc, also 37.99 ± 19.53% in male and 54.96 ± 30.58% in female CeA. In females, 3α,5α-THP reduced the MCP-1 within IBA1 and GFAP-labeled voxels in the NAc and CeA. Conversely, in males, 3α,5α-THP did not significantly alter the MCP-1 within IBA1 in NAc or with GFAP in the CeA. Furthermore, 3α,5α-THP decreased levels of IBA1 in both regions and sexes with no impact on GFAP or NeuN levels. Secondary analysis performed on data normalized to % control values indicated that no significant sex differences were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data suggest that 3α,5α-THP inhibits neuronal MCP-1 expression and decreases the proliferation of microglia in P rats. These results increase our understanding of potential mechanisms for 3α,5α-THP modulation of ethanol consumption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1693-1703"},"PeriodicalIF":3.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Articles of Public Interest","authors":"","doi":"10.1111/acer.15405","DOIUrl":"10.1111/acer.15405","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1208"},"PeriodicalIF":3.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation, oxidative stress and gut microbiome perturbation: A narrative review of mechanisms and treatment of the alcohol hangover","authors":"Benedict R. H. Turner,&nbsp;Poppy I Jenkinson,&nbsp;Marc Huttman,&nbsp;Benjamin H. Mullish","doi":"10.1111/acer.15396","DOIUrl":"10.1111/acer.15396","url":null,"abstract":"<p>Alcohol is the most widely abused substance in the world, the leading source of mortality in 15–49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1451-1465"},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}