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Impact of parental ethanol exposure on offspring memory: Sex differences in spatial and passive avoidance tasks
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-02 DOI: 10.1016/j.alcohol.2025.01.009
Amirhossein Heidari , Arman Hajikarim-Hamedani , MohammadBasir Asefi , Haniyeh Soltani , Mohammad Saber Zamani , Yekta Ghane , Setareh Rassa , Mitra Sadat-Shirazi , Mohammad-Reza Zarrindast
The impact of parental alcohol exposure on subsequent generations recently gained significant attention. Ethanol, widely consumed by humans, is known for its anxiolytic effects upon initial use. However, repeated ethanol consumption leads to cognitive dysfunction, dependence, and other physical abnormalities. In line with recent publications from our group, this study investigated the role of parental ethanol exposure—10 days prior to gestation—on learning and memory, which are critical cognitive abilities, in male and female offspring.
Adult male and female Wistar rats (n = 12) were exposed to ethanol (in drinking water) for 30 days, followed by a 10-day ethanol-free period. Each rat was then paired to mate with either an ethanol-naïve (control, n = 12) or ethanol-exposed rat, resulting in four distinct groups: (1) control male and female, (2) ethanol-exposed male and control female (P.EE), (3) ethanol-exposed female and control male (M.EE), and (4) ethanol-exposed male and female (P + M.EE). Adult male and female offspring were tested for spatial learning and memory (Morris Water Maze) and passive avoidance memory. Additionally, brain-derived neurotrophic factor (BDNF) levels in the cerebrospinal fluid were evaluated.
Results showed that spatial memory was negatively affected by parental ethanol consumption in both male and female offspring, while spatial learning was impaired only in female offspring of ethanol-exposed dams. In the passive avoidance paradigm, memory retrieval was impaired in ethanol-exposed male offspring, whereas in females, only the P + M.EE group showed a deficit in memory retention. While BDNF levels decreased in male offspring, an enhancement in BDNF was observed in female offspring of the P. EE group.
In conclusion, our findings suggest that parental ethanol exposure before conception has differential impacts on learning and memory, depending on the offspring's sex and the type of memory tested. Spatial memory was affected in both sexes (except for females in the P. EE group), while memory retrieval in the passive avoidance task remained unaffected in female offspring of the P. EE and M. EE groups. Conversely, male offspring of ethanol-exposed sires and dams exhibited deficits in passive avoidance memory. This may suggest that in memory tasks involving inhibitory cues, such as passive avoidance, female offspring of ethanol-exposed dams or sires are more resilient to memory deficits compared to male offspring. This resilience could possibly be attributed to their higher anxiety levels relative to males.
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引用次数: 0
FGF21 responses to alcohol, an insight from a comparative study in individuals with alcohol use disorder FGF21对酒精的反应--一项针对酒精使用障碍患者的比较研究的启示。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.12.001
Suthat Liangpunsakul , Lorenzo Leggio
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引用次数: 0
Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice 在雌性小鼠中,PDE4抑制可减少饮酒,但部分小胶质细胞耗竭不足以阻止应激诱导的酒精摄入量增加。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.12.004
Vernon Garcia-Rivas , Alexa R. Soares , Merrilee A. Thomas , Jessica J. Na , Asia Smith , Marina R. Picciotto , Yann S. Mineur
Stress is a major contributing factor to binge drinking and development of alcohol use disorders (AUD), particularly in women. Both stress and chronic ethanol can enhance neuroinflammatory processes, which may dysregulate limbic circuits involved in ethanol reinforcement. Clinical and preclinical studies have identified sex differences in alcohol intake in response to neuroinflammatory triggers. Since both cyclic AMP (cAMP) signaling and microglial activation contribute to neuroinflammation, we explored their contribution to stress-induced ethanol drinking in mice. To this end, we first trained C57BL/6J male and female mice to volitionally drink ethanol through a modified version of the “Drinking-in-the-Dark” paradigm. We then assessed whether exposure to foot shock stress followed by repeated exposure to the previously stress-paired context might alter volitional ethanol drinking. We observed that stress exposure resulted in a delayed increase in ethanol intake, but only in female mice. The anti-inflammatory drug Apremilast, an inhibitor of phosphodiesterase type 4 (PDE4; the primary enzyme for cAMP degradation in the brain), reduced ethanol intake and decreased preference for ethanol regardless of stress exposure in females. In contrast, a partial pharmacological depletion of microglia via PLX3397 treatment did not significantly alter baseline ethanol drinking or stress-induced ethanol drinking in female mice. This study shows that female mice are more susceptible to stress-induced ethanol drinking than males, and that this occurs even after partial microglial depletion. In addition, modulation of cAMP signaling by Apremilast administration reduced ethanol drinking regardless of stress exposure, supporting the idea that it might be useful for treatment of AUD.
压力是导致酗酒和酒精使用障碍(AUD)的主要因素,尤其是对女性而言。应激和慢性乙醇都可以增强神经炎症过程,这可能会失调参与乙醇强化的边缘回路。临床和临床前研究已经确定了酒精摄入量在神经炎症触发反应中的性别差异。由于环AMP (cAMP)信号和小胶质细胞激活都有助于神经炎症,我们探索了它们在应激诱导的小鼠乙醇饮用中的作用。为此,我们首先训练C57BL/6J雄性和雌性小鼠通过修改版本的“在黑暗中饮酒”范式自愿饮用乙醇。然后,我们评估了暴露于足部休克应激后,再重复暴露于先前的应激配对环境中,是否会改变自愿性乙醇饮酒。我们观察到,应激暴露导致乙醇摄入量延迟增加,但仅在雌性小鼠中。抗炎药阿普雷米司特是4型磷酸二酯酶(PDE4)的抑制剂;(大脑中cAMP降解的主要酶),减少了乙醇摄入量,并降低了对乙醇的偏好,无论应激暴露如何。相比之下,通过PLX3397治疗的小胶质细胞的部分药理消耗并没有显著改变雌性小鼠的基线乙醇饮用或应激性乙醇饮用。这项研究表明,雌性小鼠比雄性小鼠更容易受到应激诱导的乙醇饮酒的影响,即使在部分小胶质细胞耗竭后也会发生这种情况。此外,不管应激暴露如何,Apremilast给药对cAMP信号的调节减少了乙醇饮酒,这支持了它可能对治疗AUD有用的观点。
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引用次数: 0
Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats 服用羟考酮会阻止催产素降低大鼠的酒精摄入量。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.10.002
C.S. Wilkinson , C.G. Modrak , T.D. Thompson , R.C. Conrad , I. Leon , L.A. Knackstedt
Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague–Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 h after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 min prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.
酒精和阿片类药物的多重使用(PSU)很常见,而且往往伴随着较高的特质焦虑。催产素可降低焦虑、酒精和阿片类药物的寻求和摄取,但尚未在 PSU 的背景下进行过评估。在此,我们建立了一个连续服用羟考酮和酒精的 PSU 大鼠模型,以研究焦虑、酒精和羟考酮摄入量之间的关系,以及全身性催产素对减少酒精摄入量的功效。使用声惊吓和高架加迷宫(EPM)对雌雄 Sprague-Dawley 大鼠进行基线焦虑样行为评估。然后让大鼠连续 7 天每天 6 小时两瓶地选择使用羟考酮和/或水,然后再连续 10 天每天 24 小时五瓶地选择使用酒精(20% v/v)和/或水。接下来,单物质(羟考酮或酒精)大鼠继续每天只接触一种物质,而 PSU 大鼠则接触羟考酮和水 3 小时,然后接触酒精和水 6 小时。12 天后,大鼠在接触酒精 20 小时后接受 EPM 测试,以检查戒断相关焦虑。然后,在大鼠服用羟考酮/水后,即饮酒前 30 分钟给大鼠注射催产素(0、0.3 或 1.0 mg/kg IP)。大鼠先胃内注射羟考酮(2 毫克/千克)或水,然后胃内注射酒精(2 克/千克),并采血测定血液中的酒精含量。基线焦虑样行为的增加伴随着酒精摄入量的减少。服用羟考酮不会改变酒精摄入量,但会减少戒断时的焦虑样行为,并阻止催产素减少酒精摄入量。催产素(1 毫克/千克)可减少纯酒精条件下的酒精摄入量,这种效果在注射一次催产素后可持续数天。在无酒精条件下接受催产素治疗的大鼠比未接受治疗的大鼠显示出更高的血液酒精浓度。这些结果支持了在 PSU 啮齿动物模型中测试药物使用的必要性。
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引用次数: 0
Circulating microRNA profiling identifies microRNAs linked to prediabetes associated with alcohol dependence syndrome 循环微RNA分析确定了与酒精依赖综合征相关的糖尿病前期有关的微RNA。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.01.003
Palaniswamy Ramaswamy , Athira S V , Pratibha Misra , V.S. Chauhan , Arka Adhvaryu , Anurodh Gupta , Ankita G , Sibin M K

Background

MicroRNAs are abundant in serum and have emerged as important regulators of gene expression, implicating them in a wide range of diseases. The purpose of this study was to discover and validate serum miRNAs in prediabetes associated with alcohol dependence syndrome (ADS).

Method

Serum samples from ADS patients with or without prediabetes and normoglycemic controls were subjected to microarray. Validation of identified candidate miRNAs was performed by RT-qPCR. Additionally, GO and KEGG pathway analyses were carried out to uncover target genes anticipated to be controlled by the candidate miRNAs.

Results

Notably, 198, and 172 miRNAs were differentially expressed in ADS-patients with or without prediabetes compared to healthy controls, and 7 miRNAs in ADS-patients with prediabetes compared to ADS-normoglycemic patients, respectively. Furthermore, hsa-miR-320b and hsa-miR-3135b were differentially expressed exclusively in ADS-patients with prediabetes, and this was further validated. Interestingly, GO and KEGG pathway analysis revealed that genes predicted to be modulated by the candidates were considerably enriched in numerous diabetes-related biological processes and pathways.

Conclusion

Our findings revealed that ADS-patients with or without prediabetes have different sets of miRNAs compared to normoglycemic healthy subjects. We propose serum hsa-miR-320b and hsa-miR-3135b as potential biomarkers for the diagnosis of prediabetes in ADS-patients.
背景:微RNA在血清中含量丰富,已成为基因表达的重要调控因子,与多种疾病有关。本研究旨在发现和验证与酒精依赖综合征(ADS)相关的糖尿病前期患者的血清 miRNA:方法:对伴有或不伴有糖尿病前期的 ADS 患者和血糖正常对照组的血清样本进行芯片分析。通过 RT-qPCR 验证已确定的候选 miRNA。此外,还进行了 GO 和 KEGG 通路分析,以发现候选 miRNAs 预期控制的靶基因:值得注意的是,与健康对照组相比,有糖尿病前期或无糖尿病前期的 ADS 患者分别有 198 和 172 个 miRNAs 有差异表达;与 ADS 正常血糖患者相比,有糖尿病前期的 ADS 患者分别有 7 个 miRNAs 有差异表达。此外,hsa-miR-320b和hsa-miR-3135b只在糖尿病前期ADS患者中有差异表达,这一点得到了进一步验证。有趣的是,GO 和 KEGG 通路分析表明,候选基因预测被调节的基因在许多与糖尿病相关的生物过程和通路中都有相当大的富集:我们的研究结果表明,与血糖正常的健康受试者相比,患有或不患有糖尿病前期的 ADS 患者具有不同的 miRNAs 组。我们建议将血清中的 hsa-miR-320b 和 hsa-miR-3135b 作为诊断 ADS 患者糖尿病前期的潜在生物标记物。
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引用次数: 0
Alcohol exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin 酒精会加剧实验小鼠的创伤后应激精神病行为及其神经病理学后果:吗啉的预防作用。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.07.009
Benneth Ben-Azu , Pere-Ebi Y. Toloyai , Adaeze Adebesin , Vivian O. Ojiokor , Olusegun G. Adebayo , Aliance Romain Fokoua , Goodes E. Moke , Elo J. Ejukolemu , Ife-Oluwa O. Akpojevughe , Abdulkareem M. Abdulkadir , Ephraim Okwuchi
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2 g/kg, oral gavage) every other day, alongside daily morin (50 and 100 mg/kg) or fluoxetine (10 mg/kg) from days 8–21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin reduced TNF-α and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD-exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, and stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.
创伤后应激障碍(PTSD)和酒精使用障碍(AUD)非常普遍,并且同时存在。由于病理生理机制尚不明确,酒精如何加剧创伤后应激障碍的困境尚不清楚。此外,迄今为止,有关能有效逆转 PTSD-AUD 并发症的药理药剂的研究还很少。因此,我们设计了一种方法来研究小鼠神经保护类黄酮 Morin 的病理生理机制和药理结果。小鼠在单次长期应激(SPS)诱导后出现7天的创伤后应激障碍,在第8-21天期间,每隔一天用乙醇(2克/千克,口服)给小鼠间歇性狂饮乙醇,同时每天给小鼠服用吗啉(50和100毫克/千克)或氟西汀(10毫克/千克)。对小鼠前额皮质、纹状体和海马的创伤后应激障碍-AUD行为、下丘脑-垂体-肾上腺轴(HPA轴)功能障碍、神经化学、氧化/硝酸应激和炎症的后果进行了评估。通过减少皮质酮释放和肾上腺肥大,莫林和氟西汀可减轻小鼠因 SPS-乙醇相互作用而加剧的焦虑样行为、空间/非空间记忆缺陷、一般抑郁表型和社会应激易感性。SPS-乙醇会加剧多巴胺、5-羟色胺和谷氨酸脱羧酶的改变,以及纹状体、前足叶和海马中单胺氧化酶-B和乙酰胆碱酯酶的亢进,而吗啉可以防止这些改变。与 SPS-乙醇加重相比,吗啉能防止 TNF-α 和 IL-6 的释放、丙二醛和亚硝酸盐水平的升高,并能改善海马、前脑功能区和纹状体的抗氧化剂(谷胱甘肽、超氧化物歧化酶、过氧化氢酶)水平。总之,这些研究结果表明,AUD 加剧创伤后应激障碍的主要机制可能与 HPA 轴功能障碍加剧、神经化学降解酶上调、氧化/硝能应激和神经炎症增强有关。
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引用次数: 0
Evaluating a 30-day alcohol abstinence challenge in heavy-drinking individuals with and without chronic pain: Feasibility, safety, and perceived benefits 对患有或不患有慢性疼痛的酗酒者进行为期 30 天的戒酒挑战评估:可行性、安全性和可感知的益处。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.10.046
Dokyoung S. You , Maisa S. Ziadni , Noel Vest , Nareh Megerdichian , Tara Maronesy , Ralph J. Castro , Beth D. Darnall , Sean C. Mackey , Keith Humphreys

Introduction

To combat high-risk alcohol consumption, we introduced a 30-day alcohol abstinence challenge targeted at heavy drinkers with and without chronic pain. Our study aimed to assess the challenge's feasibility and safety and to explore its perceived benefits. Our exploratory aim was to identify participants' coping strategies during the challenge.

Methods

Our single-arm study recruited heavy drinkers from a pain clinic and a university setting (n = 34, 64.7% chronic pain). Participants underwent a modified community-based 30-day challenge, which included motivational interviewing, an individualized start date, and weekly phone check-ins.

Results

We found the 30-day challenge was feasible and safe; 72.3% of eligible heavy drinkers participated in the challenge with no serious adverse events. Most challengers (94.1%) reported some benefit from the challenge, which included improvements in alcohol withdrawal symptoms, sleep, and alcohol abstinence self-efficacy, but not in pain. We identified 25 perceived benefits and 21 coping strategies.

Conclusion

Our study confirms that a 30-day alcohol abstinence challenge is a feasible and safe intervention for heavy drinkers with and without chronic pain, yielding notable health benefits. The challenge also facilitated the development of effective coping strategies. Future studies should explore the long-term benefits of such interventions in broader outpatient settings.
简介为了打击高风险饮酒,我们针对患有或不患有慢性疼痛的酗酒者推出了一项为期 30 天的戒酒挑战。我们的研究旨在评估该挑战的可行性和安全性,并探讨其可感知的益处。我们的探索性目标是确定参与者在挑战过程中的应对策略:我们的单臂研究从疼痛诊所和大学环境中招募了酗酒者(n = 34,64.7% 为慢性疼痛患者)。参与者接受了经过修改的基于社区的 30 天挑战,其中包括动机访谈、个性化的开始日期和每周电话检查:我们发现为期 30 天的挑战是可行和安全的;72.3% 的符合条件的重度饮酒者参加了挑战,没有发生严重不良事件。大多数挑战者(94.1%)表示从挑战中获得了一些益处,其中包括戒酒症状、睡眠和戒酒自我效能的改善,但疼痛没有改善。我们确定了 25 种感知益处和 21 种应对策略:我们的研究证实,对于患有或不患有慢性疼痛的重度饮酒者来说,为期 30 天的戒酒挑战是一种可行且安全的干预措施,可为健康带来显著益处。这项挑战还有助于制定有效的应对策略。未来的研究应探索此类干预措施在更广泛的门诊环境中的长期益处。
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引用次数: 0
The alcohol exposome 酒精暴露。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.12.003
Nousha H. Sabet , Todd A. Wyatt
Science is now in a new era of exposome research that strives to build a more all-inclusive, panoramic view in the quest for answers; this is especially true in the field of toxicology. Alcohol exposure researchers have been examining the multivariate co-exposures that may either exacerbate or initiate alcohol-related tissue/organ injuries. This manuscript presents selected key variables that represent the Alcohol Exposome. The primary variables that make up the Alcohol Exposome can include comorbidities such as cigarettes, poor diet, occupational hazards, environmental hazards, infectious agents, and aging. In addition to representing multiple factors, the Alcohol Exposome examines the various types of intercellular communications that are carried from one organ system to another and may greatly impact the types of injuries and metabolites caused by alcohol exposure. The intent of defining the Alcohol Exposome is to bring the newly expanded definition of Exposomics, meaning the study of the exposome, to the field of alcohol research and to emphasize the need for examining research results in a non-isolated environment representing a more relevant manner in which all human physiology exists.
科学现在正处于一个暴露研究的新时代,在寻求答案的过程中,努力建立一个更全面、更全面的观点;在毒理学领域尤其如此。酒精暴露研究人员一直在研究可能加剧或引发酒精相关组织/器官损伤的多变量共同暴露。这份手稿提出了代表酒精暴露的选定关键变量。构成酒精暴露体的主要变量包括合并症,如吸烟、不良饮食、职业危害、环境危害、传染病和衰老。除了代表多种因素外,酒精暴露还检查了从一个器官系统到另一个器官系统的各种类型的细胞间通讯,这些通讯可能极大地影响酒精暴露引起的损伤和代谢物的类型。定义酒精接触体的目的是将新扩展的暴露组学(即对接触体的研究)的定义引入酒精研究领域,并强调需要在非孤立环境中检验研究结果,这种环境代表了所有人类生理学都存在的更相关的方式。
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引用次数: 0
Investigation of serum BDNF levels in alcohol withdrawal syndrome with and without other medical co-morbidities 调查有无其他并发症的酒精戒断综合征患者的血清 BDNF 水平。
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2023.12.006
Magda Malewska-Kasprzak , Agnieszka Permoda-Pachuta , Maria Skibińska , Marta Malinowska-Kubiak , Filip Rybakowski , Monika Dmitrzak-Węglarz

Introduction

Consequences of alcohol use disorder (AUD) are associated with mental and somatic burdens that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). So far, biomarkers for tracking abstinence syndrome that are useful in clinical practice have yet to be detected. Current research focuses on brain-derived neurotrophic factor (BDNF) effects on neurogenesis, modulation of plasticity, and its role in the pathogenesis of AWS and DTs.

Aims

The present study aimed to assess pro-BDNF and BDNF concentrations in a group of patients with AWS. Changes in BDNF and prof-BDNF were also evaluated with attention to subgroups of patients with coexisting mental and somatic disorders, with a particular emphasis on the presence or absence of DTs.

Results

The AWS group had a higher concentration of BDNF and a lower concentration of pro-BDNF compared to the control group, and BDNF increased during 7 days of hospitalisation. Patients with comorbid psychiatric disorders had higher levels of pro-BDNF than those without disease and also had higher levels of BDNF at the end of the study than at the beginning. On the other hand, patients with coexisting somatic diseases had higher levels of pro-BDNF at the beginning than at the end of the study, while patients with delirium had higher BDNF levels at the end of the study than at the beginning.

Conclusions

The obtained results indicate that pro-BDNF and BDNF may be useful markers for the course of withdrawal syndrome. In particular, BDNF showed an association with the development of delirium complications. The authors are aware of several limitations of the work only men in the SG, different age between SG and CG.
酒精使用障碍(AUD)的后果与导致酒精戒断综合征(AWS)的精神和身体负担相关,其中30%的AWS病例导致危及生命的震颤谵妄(DTs)。到目前为止,在临床实践中有用的追踪戒断综合征的生物标志物尚未被发现。目前的研究主要集中在脑源性神经营养因子(BDNF)对神经发生的影响、可塑性的调节及其在AWS和DTs发病机制中的作用。目的:本研究旨在评估一组AWS患者中BDNF和BDNF的浓度。BDNF和pro -BDNF的变化也被评估,并关注患有精神和躯体疾病的患者亚组,特别强调是否存在DTs。结果:与对照组相比,AWS组BDNF浓度较高,pro-BDNF浓度较低,且BDNF在住院7天内升高。患有精神疾病的患者比没有疾病的患者有更高水平的BDNF,并且在研究结束时比开始时有更高水平的BDNF。另一方面,患有共存躯体疾病的患者在研究开始时的BDNF水平高于研究结束时,而谵妄患者在研究结束时的BDNF水平高于研究开始时。结论:BDNF pro和BDNF可能是戒断综合征病程的有用标志物。特别是,BDNF显示与谵妄并发症的发展有关。作者意识到这项研究的局限性,即研究对象仅为男性,研究对象与研究对象的年龄不同。
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引用次数: 0
Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats 单次和多次暴饮暴食暴露乙醇戒断对青春期大鼠社交焦虑样行为和神经肽基因表达的性别依赖性影响
IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.alcohol.2024.10.001
Peter T. Penta, Susanna Villarreal, Caitlin I. Rameas, Ella C. Collins, Trevor T. Towner, Elena I. Varlinskaya, David F. Werner
Ethanol withdrawal sensitivity is a risk factor for the development of alcohol use disorder. Heavy episodic drinking during adolescence often encompasses repeated periods of withdrawal. Adolescent intermittent ethanol exposure of laboratory rodents produces several neurobiological deficits that differ between sexes, but the sensitivity to withdrawal as a contributor to the observed sex differences is not clear. The current study assessed the impact of acute withdrawal from a single- and repeated binge ethanol episodes during adolescence as well as protracted abstinence from repeated binge episodes on social anxiety-like behavior (indexed via significant decreases of social investigation) as well as oxytocin (OXT) and vasopressin (AVP) system gene expression in the hypothalamus (HYP) and central amygdala (CeA) in male and female Sprague Dawley rats. Females displayed social anxiety-like behavior during withdrawal from a single binge episode, whereas both sexes showed social anxiety-like changes following acute withdrawal from repeated binge episodes. After a period of protracted abstinence, only males still displayed ethanol-associated social alterations. Analysis of gene expression in separate, non-socially tested subjects revealed that withdrawal from repeated binge episodes during adolescence increased AVP gene expression in the HYP of males and decreased it in females. Males also displayed increased AVP and OXTR gene expression during acute withdrawal from repeated binge episodes in the CeA, with these changes persisting into adulthood. Together, these findings suggest that adolescent females are sensitive to withdrawal from both acute and repeated ethanol exposures, whereas males are sensitive to withdrawal from repeated ethanol exposures, with affective and transcriptional changes persisting into adulthood.
乙醇戒断敏感性是导致酒精使用障碍的一个危险因素。青春期的大量偶发性饮酒往往包括反复的戒断期。实验室啮齿类动物在青春期间歇性接触乙醇会产生多种神经生物学缺陷,这些缺陷在性别上存在差异,但对戒断的敏感性是导致观察到的性别差异的一个因素,这一点尚不清楚。本研究评估了青春期单次和多次暴饮乙醇的急性戒断以及多次暴饮乙醇的长期戒断对雌雄 Sprague Dawley 大鼠社交焦虑样行为(以社交调查的显著减少为指标)以及下丘脑(HYP)和中央杏仁核(CeA)中催产素(OXT)和血管加压素(AVP)系统基因表达的影响。雌性大鼠在单次暴饮暴食后的戒断过程中表现出类似社交焦虑的行为,而雌雄大鼠在多次暴饮暴食后的急性戒断过程中都表现出类似社交焦虑的变化。在长期戒断后,只有雄性大鼠仍表现出与乙醇相关的社交变化。对单独的、非社交测试对象的基因表达分析表明,在青春期因反复酗酒而戒断后,男性 HYP 中的 AVP 基因表达增加,而女性则减少。在CeA中,男性在急性戒断重复酗酒发作时也显示出AVP和OXTR基因表达增加,这些变化一直持续到成年。这些研究结果表明,青春期女性对急性和反复暴露于乙醇的戒断敏感,而男性对反复暴露于乙醇的戒断敏感,其情感和转录变化会持续到成年。
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Alcohol
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