{"title":"Effects of daridorexant on rest/wake activity patterns and drinking in adult rats exposed to chronic ethanol vapor in adolescence","authors":"L.R. Amodeo , D.N. Wills , J. Benedict , C.L. Ehlers","doi":"10.1016/j.alcohol.2025.01.006","DOIUrl":"10.1016/j.alcohol.2025.01.006","url":null,"abstract":"<div><div>Disturbance in sleep and activity rhythms are significant health risks associated with alcohol use during adolescence. Many investigators support the theory of a reciprocal relationship between disrupted circadian rhythms, sleep patterns, and alcohol usage. However, in human studies it is difficult to disentangle other factors (i.e. lifestyle, psychiatric, genetic) when determining what is causal in the relationship between substance use and sleep/activity disruptions. To this end, we used an animal model of adolescent alcohol exposure whereby male and female Wistar rats are exposed to 5 weeks of intermittent alcohol vapor during adolescence (P22-P57). Five days after ethanol vapor rats were allowed to select to drink alcohol or water in a two-bottle choice procedure for a period of 5 h, 4 days a week for 6 weeks. Activity data was collected using a “Fitbit-like” device during vapor exposure, during acute withdrawal, and after 3 weeks of protracted withdrawal. Significant changes in rest/wake activity and circadian measures were seen during 24-h withdrawal and after 3 weeks of withdrawal. Four weeks following withdrawal, the effects of the dual orexin antagonist, Daridorexant, (DAX 30 mg, 100 mg, or vehicle control), on alcohol drinking and rest and activity rhythms were assessed over a 24 h period. Both daridorexant doses led to changes in circadian measures and rest/wake activity patterns. These results showed that daridorexant reduced activity, but it did not improve rest quality as measured by the mean inactive episode duration and inactive fragmentation ratio. Additionally, we did not find a significant difference in drinking behavior in animals treated with the orexin antagonist. Thus, it appears that data from this animal model do not support the use of this drug to improve adolescent alcohol-induced sleep disturbance and/or to decrease alcohol drinking.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"124 ","pages":"Pages 35-46"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-05-01Epub Date: 2023-09-09DOI: 10.1016/j.alcohol.2023.09.002
Tawonga Mkochi , Agatha Chitanda , Evaristar Kudowa , Khumbo Bula , Jimmy Msolola , Immaculate Chamangwana , Mitch Matoga
{"title":"Assessing the adoption, acceptability and fidelity of the alcohol use disorders test for alcohol use disorders screening in HIV clinics in Malawi","authors":"Tawonga Mkochi , Agatha Chitanda , Evaristar Kudowa , Khumbo Bula , Jimmy Msolola , Immaculate Chamangwana , Mitch Matoga","doi":"10.1016/j.alcohol.2023.09.002","DOIUrl":"10.1016/j.alcohol.2023.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol use disorders (AUD) are a common cause of poor treatment outcomes among people with HIV (PWH). In Malawi, routine screening for AUD among PWH is unavailable. We piloted the utility of the Alcohol Use Disorders Identification Test (AUDIT) in screening for AUD among PWH and assessed its adoption, acceptability, and fidelity in HIV clinics in Malawi.</div></div><div><h3>Methods</h3><div>We implemented the AUDIT tool at Mchinji, Kapiri, and Kochirira hospitals in Mchinji District between April and May 2021. Participants with AUD were defined and classified based on World Health Organization (WHO) classification as low risk, harmful/hazardous alcohol use, or alcohol dependence. We calculated the prevalence of AUD, the proportion of providers who conducted AUD screening (adoption), and the proportion of providers who conducted AUD screening as intended (fidelity) and compared the results between clinics. Lastly, we assessed acceptability through a survey among providers.</div></div><div><h3>Results</h3><div>Out of 2036 PWH, 875 (43%) were screened for AUD and 51% were female, mean age was 41 years (SD ± 12), and 338 (39%) had AUD. Adoption was highest at Mchinji (58%) compared to Kapiri (31%) and Kochirira (29%) (<em>p</em> < 0.001). Overall fidelity was 96%, and it was highest at Kapiri (99%) compared to Mchinji (95%) and Kochirira (98%) (<em>p</em> = 0.01). AUD screening with AUDIT was highly acceptable as most providers agreed or completely agreed that the AUDIT was important (100%), easy to use (96%), satisfactory (96%), agreed to continue using (61%), and recommended it for other facilities in the district (100%).</div></div><div><h3>Conclusion</h3><div>People with AUD were common among PWH. While the adoption of AUDIT for AUD screening was moderate, acceptability and fidelity were high. The impact of AUD on HIV treatment outcomes needs to be assessed to determine the role of routine AUD screening in HIV clinics in Malawi.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"124 ","pages":"Pages 1-5"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2025-01-04DOI: 10.1016/j.alcohol.2025.01.001
Justin J. Verlinden , Mairead E. Moloney , Olga A. Vsevolozhskaya , Lauren N. Whitehurst , Jessica Weafer
{"title":"Indirect effects of perceived stress and depression on the relationship between insomnia symptoms and hazardous drinking","authors":"Justin J. Verlinden , Mairead E. Moloney , Olga A. Vsevolozhskaya , Lauren N. Whitehurst , Jessica Weafer","doi":"10.1016/j.alcohol.2025.01.001","DOIUrl":"10.1016/j.alcohol.2025.01.001","url":null,"abstract":"<div><div>Insomnia is a risk factor for hazardous drinking, yet the mechanisms underlying this risk are not well characterized. Two factors that might contribute to the relationship between insomnia and drinking are stress and depression. Insomnia is strongly associated with increased stress and depression, which are, in turn, strongly linked to hazardous drinking. Here we conducted a preliminary investigation to determine whether perceived stress and depression indirectly explain the relationship between insomnia and hazardous drinking. Heavy drinkers with self-reported insomnia (n = 405: 270 women, 134 men, 1 non-binary) completed self-report measures of hazardous drinking, insomnia, perceived stress, and depression. Results from our primary cross-sectional parallel mediation model with insomnia as the predictor and hazardous drinking as the outcome showed that, when accounting for the influence of both perceived stress and depression, there was a partial indirect effect of insomnia on hazardous drinking through perceived stress, 95% CI [0.014, 0.205], but not depression, 95% CI [-0.080, 0.172]. In our competing cross-sectional parallel mediation model with hazardous drinking as the predictor and insomnia as the outcome, there was a partial indirect effect of hazardous drinking on insomnia through depression 95% CI [0.016, 0.059], but not perceived stress 95% CI: [-0.026, 0.011]. Results suggest that insomnia may be related to hazardous drinking through its effects on stress and that hazardous drinking may be related to insomnia through its effects on depression. These findings lay the groundwork for future longitudinal studies assessing the causal roles of stress and depression in the insomnia-AUD relationship.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 1-9"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-11-22DOI: 10.1016/j.alcohol.2024.11.003
T.L. Verplaetse , R.F. Carretta , C.A. Struble , B. Pittman , W. Roberts , Y. Zakiniaeiz , M.R. Peltier , S.A. McKee
{"title":"Gender differences in alcohol use disorder trends from 2009–2019: An intersectional analysis","authors":"T.L. Verplaetse , R.F. Carretta , C.A. Struble , B. Pittman , W. Roberts , Y. Zakiniaeiz , M.R. Peltier , S.A. McKee","doi":"10.1016/j.alcohol.2024.11.003","DOIUrl":"10.1016/j.alcohol.2024.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Trend estimates from national surveys over the last 20 years have suggested converging rates of alcohol use over time between adult men and women. However, limited research has utilized an intersectional lens to examine how sociodemographic characteristics influence gender differences in these trends.</div></div><div><h3>Methods</h3><div>The current study used data from the National Survey on Drug Use and Health (NSDUH) to examine whether gender intersected with race/ethnicity, age, education level, marital status, employment status, household income, and urbanicity on temporal trends (2009–2019) in alcohol use disorder (AUD). Logistic regression and linear trend analyses were conducted to examine interaction effects of sociodemographic variables and changes in rates of AUD over time in males and females.</div></div><div><h3>Results</h3><div>We observed decreasing rates of AUD over time in males and females, with larger declines in males (<em>p</em> = 0.01; OR = 0.96 in males vs. OR = 0.98 in females). We identified subpopulations of females that demonstrated little or no reductions during this timeframe (2009–2019), which varied by race/ethnicity, age, marital status, employment, and income but not by education or urbanicity. In adults aged 49 years and younger (overall <em>p</em> = 0.02; ages 18–25 OR = 0.92 in males vs. 0.96 in females, ages 26–29 OR = 0.97 in males vs. OR = 0.99 in females), and in those employed (overall <em>p</em> = 0.05; OR = 0.96 in males vs. OR = 0.99 in females), women demonstrated smaller declines in comparison to men. Additionally, women who reported that they were Black (<em>p</em> = 0.006; OR = 0.94 in males vs. OR = 1 in females), single (<em>p</em> = 0.009; OR = 0.94 in males vs. 0.96 in females) or earning between $20,000 and $49,000 (<em>p</em> = 0.012; OR = 0.96 in males vs. 0.98 in females), had smaller or no declines in AUD in compared to men with the same demographic characteristic.</div></div><div><h3>Conclusions</h3><div>Our findings provide support for converging rates of AUD between genders and newly identify subpopulations of females that may be at heightened risk.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 101-107"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-11-12DOI: 10.1016/j.alcohol.2024.11.002
Andressa Raphaely de Lima Silva , Maria Letícia Santos Carnaúba da Silva , Jadson Freitas da Silva , Katarine Evelyn Falcão e Falcão , James A. Marrs , Marilia Ribeiro Sales Cadena , Pabyton Gonçalves Cadena
{"title":"Single essential oils and their binary mixtures protect against ethanol-induced defects in a zebrafish fetal alcohol spectrum disorder model at the same level as folic acid","authors":"Andressa Raphaely de Lima Silva , Maria Letícia Santos Carnaúba da Silva , Jadson Freitas da Silva , Katarine Evelyn Falcão e Falcão , James A. Marrs , Marilia Ribeiro Sales Cadena , Pabyton Gonçalves Cadena","doi":"10.1016/j.alcohol.2024.11.002","DOIUrl":"10.1016/j.alcohol.2024.11.002","url":null,"abstract":"<div><div>This study evaluated protective effects of clove (SEO), thyme white (TEO), oregano (OEO), and caraway (CEO) essential oils (EOs), and their binary mixtures, in a zebrafish fetal alcohol spectrum disorder model. Furthermore, folic acid (FA) was used for comparison as it had previously shown protection against ethanol (EtOH)-induced defects. The co-exposure of zebrafish embryos to EtOH (150 mM) and FA (75 μM) or EOs and their binary mixtures (0.5–1 mg/L) was carried out during 6 or 22 h postfertilization (hpf). Different developmental endpoints (epiboly measurement, survival rate at 24 hpf, embryonic developmental progression measurement at 24 hpf, larval development at 48–96 hpf, and hatching rate at 72–96 hpf) were evaluated at 8–96 hpf. EtOH exposure reduced epiboly. Only FA and the SEO + TEO binary mixture protected against these defects, and SEO and TEO single exposure showed partial protection. Therefore, these groups were chosen for subsequent experiments. At 24 hpf, EtOH showed developmental delay and hatching rate was delayed at 72 hpf. FA, SEO, TEO, and SEO + TEO partially protected against these defects. This study supports the conclusion that FA partially protects against EtOH-induced defects. SEO and TEO single exposure partially protect against EtOH-induced defects. However, the binary mixture of SEO + TEO was more effective, showing similar efficacy as FA.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 77-86"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2025-01-19DOI: 10.1016/j.alcohol.2025.01.003
Katie Witkiewitz , Lorenzo Leggio
{"title":"Sex and gender differences in alcohol use disorder: Quo Vadis?","authors":"Katie Witkiewitz , Lorenzo Leggio","doi":"10.1016/j.alcohol.2025.01.003","DOIUrl":"10.1016/j.alcohol.2025.01.003","url":null,"abstract":"","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 121-125"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-12-24DOI: 10.1016/j.alcohol.2024.12.005
Nathaniel Albright , Ethan Morgan
{"title":"Assessing the relationship between mental health and AUDIT score among older sexual and gender minorities","authors":"Nathaniel Albright , Ethan Morgan","doi":"10.1016/j.alcohol.2024.12.005","DOIUrl":"10.1016/j.alcohol.2024.12.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Alcohol use, and its relationship with mental health outcomes, remains a public health priority. Yet, little research has focused on this association among aging sexual and gender minority (SGM) populations with even less dedicated to the unique issues of those aging with HIV, a gap we begin to fill here.</div></div><div><h3>Methods</h3><div>Data for this analysis originated from the Columbus Healthy Aging Project (CHAP), a cross-sectional survey among adults ≥50 years who reside in the Columbus, Ohio. Multivariable linear regression models were utilized to assess the relationship between alcohol use (via AUDIT score) and several mental health outcomes (e.g., depression, anxiety, perceived stress, and sexual orientation microaggressions), adjusting for demographic characteristics and other risk factors. Models were assessed for moderation by self-reported HIV status.</div></div><div><h3>Results</h3><div>Among the entire sample (N = 787), mean perceived stress score was 18.2 (SD = 5.5), mean anxiety score was 9.1 (5.9), and mean depression score was 9.9 (SD = 6.7). 32 (7.4%) self-reported as PLWH. Among those reporting any alcohol use, mean AUDIT score use was 10.5 (SD = 10.9). Each of the mental health outcome measures were positively associated with AUDIT score. Meanwhile, there was significant moderation of each of the mental health outcome measures by HIV status, suggesting a stronger association with AUDIT score in each case.</div></div><div><h3>Conclusion</h3><div>Our results suggest that there are broad stressors impacting alcohol use not only among older SGM broadly but in particular among PLWH. Although a diverse set of results, these data highlight the need for more research on alcohol use among aging SGM populations, particularly PLWH and those identifying as a different gender identity.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 51-56"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-12-20DOI: 10.1016/j.alcohol.2024.12.006
J. Daniel Obray , Adam R. Denton , Jayda Carroll-Deaton , Kristin Marquardt , L. Judson Chandler , Michael D. Scofield
{"title":"Enhanced fear extinction through infralimbic perineuronal net digestion: The modulatory role of adolescent alcohol exposure","authors":"J. Daniel Obray , Adam R. Denton , Jayda Carroll-Deaton , Kristin Marquardt , L. Judson Chandler , Michael D. Scofield","doi":"10.1016/j.alcohol.2024.12.006","DOIUrl":"10.1016/j.alcohol.2024.12.006","url":null,"abstract":"<div><div>Perineuronal nets (PNNs) are specialized components of the extracellular matrix that play a critical role in learning and memory. In a Pavlovian fear conditioning paradigm, degradation of PNNs affects the formation and storage of fear memories. This study examined the impact of adolescent intermittent ethanol (AIE) exposure by vapor inhalation on the expression of PNNs in the adult rat prelimbic (PrL) and infralimbic (IfL) subregions of the medial prefrontal cortex. Results indicated that following AIE, the total number of PNN positive cells in the PrL cortex increased in layer II/III but did not change in layer V. Conversely, in the IfL cortex, the number of PNN positive cells decreased in layer V, with no change in layer II/III. In addition, the intensity of PNN staining was significantly altered by AIE exposure, which narrowed the distribution of signal intensity, reducing the number of high and low intensity PNNs. Given these changes in PNNs, the next experiment assessed the effects of AIE and PNN digestion on extinction of a conditioned fear memory. In Air control rats, digestion of PNNs by bilateral infusion of Chondroitinase ABC (ChABC) into the IfL cortex enhanced fear extinction and reduced contextual fear renewal. In contrast, both fear extinction learning and contextual fear renewal remained unchanged following PNN digestion in AIE exposed rats. These results highlight the sensitivity of prefrontal PNNs to adolescent alcohol exposure and suggest that ChABC-induced plasticity is reduced in the IfL cortex following AIE exposure.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 57-67"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-03-13DOI: 10.1016/j.alcohol.2024.03.007
S. Washburn , K. Nation , T. Cudd , M. Stanton , C. Goodlett
{"title":"Gestational choline supplementation ameliorates T-maze reversal learning deficits induced by first trimester binge alcohol exposure in weanling lambs","authors":"S. Washburn , K. Nation , T. Cudd , M. Stanton , C. Goodlett","doi":"10.1016/j.alcohol.2024.03.007","DOIUrl":"10.1016/j.alcohol.2024.03.007","url":null,"abstract":"<div><div>In rodent models of fetal alcohol spectrum disorders (FASD), cognitive deficits are implicated in impaired T-maze spatial reversal learning. Rat studies have indicated supplemental administration of choline during the developmental period of alcohol exposure can ameliorate spatial reversal deficits. This study tested whether beneficial effects of prenatal choline supplementation could be confirmed in a sheep model of binge exposure in the first trimester equivalent. Two hypotheses were tested: 1) alcohol exposure would produce deficits in reversal of a T-maze position discrimination; and 2) gestational dietary supplementation of choline would ameliorate those deficits. Mated ewes were assigned to one of seven groups—a normal control (NC) group or one of six infusion treatment groups: saline control (SC; isotonic saline), saline control plus choline (SC-CH; isotonic saline plus choline, 10 mg/kg administered orally throughout each day of gestation), binge alcohol (BA; 1.75 g/kg alcohol per infusion day), binge alcohol plus choline (BA-CH; 1.75 g/kg/day alcohol plus choline), heavy binge alcohol (HBA; 2.5 g/kg/day alcohol), or heavy binge alcohol plus choline (HBA-CH; 2.5 g/kg/day alcohol plus choline). The alcohol infusions modeled a weekend binge drinking pattern over the first trimester-equivalent (gestational day 4–41). T-maze training began at 12 weeks of age, with daily sessions occurring 5 days/week. Lambs were given five days of habituation training, followed by five days of position discrimination training (3 trials per daily session, intertrial interval of 3 h, reinforced side randomly assigned across subjects). Lambs were then given 10 days of training on the reversal task. There was no difference among groups during acquisition. Alcohol impaired reversal learning, and choline supplementation mitigated these deficits in the HBA-CH group. These results suggest that maternal dietary choline supplementation can ameliorate or prevent some impairments of executive function in a sheep model of FASD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 109-120"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AlcoholPub Date : 2025-03-01Epub Date: 2024-09-06DOI: 10.1016/j.alcohol.2024.09.002
Ilknur Dursun , Nur Damla Korkmaz , Sinem Firtina , Muhammed Salih Erkoyuncu , Fahri Akbas , Birsen Elibol
{"title":"Exploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development","authors":"Ilknur Dursun , Nur Damla Korkmaz , Sinem Firtina , Muhammed Salih Erkoyuncu , Fahri Akbas , Birsen Elibol","doi":"10.1016/j.alcohol.2024.09.002","DOIUrl":"10.1016/j.alcohol.2024.09.002","url":null,"abstract":"<div><div>Early developmental exposure to alcohol has been implicated in adverse effects on the brain, often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol consumption during pregnancy has been linked to the manifestation of mental health disorders, such as depression and anxiety, in subsequent generations. These mood disturbances may be attributed to alterations in protein expressions related to depression and anxiety within the hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal exposure to alcohol induces changes in hippocampus, potentially through epigenetic modifications. The <em>FKBP5</em> gene, known to modulate the stress response, is particularly relevant in this context. We postulate that alcohol-induced methylation of the <em>FKBP5</em> gene disrupts HPA axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation control pups were subjected to the same procedures without ethanol or milk, and a non-intubated control group included. Anxiety-like and depressive-like behaviors were assessed using the open field test, plus maze test, forced swim test, and tail suspension test when the pups reached 3 months of age. For epigenetic analysis of the <em>FKBP5</em> gene, genomic DNA was isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as verified by behavioral assessments. Methylation profiling revealed higher rates of methylation within the stress-associated gene <em>FKBP5</em> in both the early postnatal alcohol-exposed cohort (13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying the observed behavioral alterations, implicating <em>FKBP5</em> methylation as a candidate mediator of the increased vulnerability to mood disorders following early postnatal alcohol exposure.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"123 ","pages":"Pages 11-17"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}