Alcoholism, clinical and experimental research最新文献_第10页

Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System. 乙醇对中枢神经系统先天免疫反应的影响。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-11-01 DOI: 10.1111/acer.13208

J. Montesinos, S. Alfonso-Loeches, C. Guerri

{"title":"Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System.","authors":"J. Montesinos, S. Alfonso-Loeches, C. Guerri","doi":"10.1111/acer.13208","DOIUrl":"https://doi.org/10.1111/acer.13208","url":null,"abstract":"The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation. This review focuses on evidence that indicates the participation of TLRs and the inflammasome NLRs signaling response in many effects of EtOH on the CNS, such as neuroinflammation associated with brain damage, cognitive and behavioral dysfunction, and adolescent brain development alterations. It also reviews findings that indicate the role of TLR4-dependent signaling immune molecules in alcohol consumption, reward, and addiction. The research data suggest that overactivation of TLR4 or NLRs increases pro-inflammatory cytokines and mediators to cause neural damage in the cerebral cortex and hippocampus, while modest TLR4 activation, along with the generation of certain cytokines and chemokines in specific brain areas (e.g., amygdala, ventral tegmental area), modulate neurotransmission, alcohol drinking, and alcohol rewards. Elimination of TLR4 and NLRP3 abolishes many neuroimmune effects of EtOH. Despite much progress being made in this area, there are some research gaps and unanswered questions that this review discusses. Finally, potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also evaluated.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"29 1","pages":"2260-2270"},"PeriodicalIF":3.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88458082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 146

Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus-Infected Liver Cells by Up-Regulating USP18. 乙醛通过上调USP18干扰丙型肝炎病毒感染肝细胞中的干扰素α信号

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-11-01 DOI: 10.1111/acer.13226

M. Ganesan, L. Poluektova, D. Tuma, K. Kharbanda, N. Osna

{"title":"Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus-Infected Liver Cells by Up-Regulating USP18.","authors":"M. Ganesan, L. Poluektova, D. Tuma, K. Kharbanda, N. Osna","doi":"10.1111/acer.13226","DOIUrl":"https://doi.org/10.1111/acer.13226","url":null,"abstract":"BACKGROUND\u0000Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and worsens disease outcomes. The exact reasons are not clear yet, but they might be partially attributed to the ability of alcohol to further suppress the innate immunity. Innate immunity is known to be already decreased by HCV in liver cells.\u0000\u0000\u0000METHODS\u0000In this study, we aimed to explore the mechanisms of how alcohol metabolism dysregulates IFNα signaling (STAT1 phosphorylation) in HCV+ hepatoma cells. To this end, CYP2E1+ Huh7.5 cells were infected with HCV and exposed to the acetaldehyde (Ach) generating system (AGS).\u0000\u0000\u0000RESULTS\u0000Continuously produced Ach suppressed IFNα-induced STAT1 phosphorylation, but increased the level of a protease, USP18 (both measured by Western blot), which interferes with IFNα signaling. Induction of USP18 by Ach was confirmed in primary human hepatocyte cultures and in livers of ethanol-fed HCV transgenic mice. Silencing of USP18 by specific siRNA attenuated the pSTAT1 suppression by Ach. The mechanism by which Ach down-regulates pSTAT1 is related to an enhanced interaction between IFNαR2 and USP18 that finally dysregulates the cross talk between the IFN receptor on the cell surface and STAT1. Furthermore, Ach decreases ISGylation of STAT1 (protein conjugation of a small ubiquitin-like modifier, ISG15, Western blot), which preserves STAT1 activation. Suppressed ISGylation leads to an increase in STAT1 K48 polyubiquitination which allows pSTAT1 degrading by proteasome.\u0000\u0000\u0000CONCLUSIONS\u0000We conclude that Ach disrupts IFNα-induced STAT1 phosphorylation by the up-regulation of USP18 to block the innate immunity protection in HCV-infected liver cells, thereby contributing to HCV-alcohol pathogenesis. This, in part, may explain the mechanism of HCV-infection exacerbation/progression in alcohol-abusing patients.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"17 1","pages":"2329-2338"},"PeriodicalIF":3.2,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85059240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

The Formation, Elimination, Interpretation, and Future Research Needs of Phosphatidylethanol for Research Studies and Clinical Practice. 磷脂酰乙醇在研究和临床实践中的形成、消除、解释和未来的研究需求。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-11-01 DOI: 10.1111/acer.13213

J. Hahn, R. Anton, M. Javors

引用次数: 56

Disruption of Integrated Neuronal and Astrocytic Signaling Contributes to Alcohol Use Disorder. 综合神经元和星形细胞信号的破坏有助于酒精使用障碍。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-11-01 DOI: 10.1111/acer.13227

D. Lindberg, D. Choi

引用次数: 0

Reproducibility of Experiments with Laboratory Animals: What Should We Do Now? 实验动物实验的可重复性:我们现在该怎么做?

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-11-01 DOI: 10.1111/acer.13228

J. Crabbe

引用次数: 8

Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1 Phosphorylation. 慢性尼古丁暴露的戒断对酒精刺激的GluA1磷酸化产生区域特异性耐受性。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-10-31 DOI: 10.1111/acer.13258

M. A. McGinn, Rod I. Paulsen, Christy A. Itoga, Muhammad A Farooq, Jonathan E Reppel, K. Edwards, Annie M. Whitaker, N. Gilpin, Scott Edwards

{"title":"Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1 Phosphorylation.","authors":"M. A. McGinn, Rod I. Paulsen, Christy A. Itoga, Muhammad A Farooq, Jonathan E Reppel, K. Edwards, Annie M. Whitaker, N. Gilpin, Scott Edwards","doi":"10.1111/acer.13258","DOIUrl":"https://doi.org/10.1111/acer.13258","url":null,"abstract":"BACKGROUND\u0000Nicotine use increases alcohol drinking, suggesting that the combination of these drugs may produce synergistic effects in activating reward circuitry. Alternatively, use of either of these drugs may facilitate the development of cross-tolerance to the other to promote intake escalation.\u0000\u0000\u0000METHODS\u0000In this study, adult male Wistar rats were chronically exposed to room air or chronic, intermittent nicotine vapor, which has been shown to produce symptoms of nicotine dependence as evidenced by elevated nicotine self-administration and a host of somatic and motivational withdrawal symptoms. We examined regional neuroadaptations in nicotine-experienced versus nonexperienced animals, focusing on changes in phosphorylation of the AMPA glutamate channel subunit GluA1 in reward-related brain regions as excitatory neuroadaptations are heavily implicated in both alcohol and nicotine addiction.\u0000\u0000\u0000RESULTS\u0000During withdrawal, nicotine exposure and alcohol challenge (1 g/kg) interactively produced neuroadaptations in GluA1 phosphorylation in a brain region-dependent manner. Alcohol robustly increased protein kinase A-mediated phosphorylation of GluA1 at serine 845 in multiple regions. However, this neuroadaptation was largely absent in 3 areas (dorsomedial prefrontal cortex, dorsal striatum, and central amygdala) in nicotine-experienced animals. This interactive effect suggests a molecular tolerance to alcohol-stimulated phosphorylation of GluA1 in the context of nicotine dependence.\u0000\u0000\u0000CONCLUSIONS\u0000Nicotine may modify the rewarding or reinforcing effects of alcohol by altering glutamate signaling in a region-specific manner, thereby leading to increased drinking in heavy smokers.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"1 1","pages":"2537-2547"},"PeriodicalIF":3.2,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84841440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Metabolomics Analysis Revealed Distinct Cyclic Changes of Metabolites Altered by Chronic Ethanol-Plus-Binge and Shp Deficiency. 代谢组学分析显示，慢性酒精+暴食和Shp缺乏改变了代谢物的明显循环变化。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-10-28 DOI: 10.1111/acer.13257

Melanie Tran, Zhihong Yang, S. Liangpunsakul, Li Wang

{"title":"Metabolomics Analysis Revealed Distinct Cyclic Changes of Metabolites Altered by Chronic Ethanol-Plus-Binge and Shp Deficiency.","authors":"Melanie Tran, Zhihong Yang, S. Liangpunsakul, Li Wang","doi":"10.1111/acer.13257","DOIUrl":"https://doi.org/10.1111/acer.13257","url":null,"abstract":"BACKGROUND\u0000Chronic ethanol (EtOH) consumption causes alcoholic liver disease (ALD), and disruption of the circadian system facilitates the development of ALD. Small heterodimer partner (SHP) is a nuclear receptor and critical regulator of hepatic lipid metabolism. This study aimed at depicting circadian metabolomes altered by chronic EtOH-plus-binge and Shp deficiency using high-throughput metabolomics.\u0000\u0000\u0000METHODS\u0000Wild-type (WT) C57BL/6 and Shp-/- mice were fed the control diet (CD) or Lieber-DeCarli EtOH liquid diet (ED) for 10 days followed by a single bout of maltose (CD + M) or EtOH (ED + E) binge on the 11th day. Serum and liver were collected over a 24-hour light/dark (LD) cycle at Zeitgeber time ZT12, ZT18, ZT0, and ZT6, and metabolomics was performed using gas chromatography-mass spectrometry.\u0000\u0000\u0000RESULTS\u0000A total of 110 metabolites were identified in liver and of those 80 were also present in serum from pathways of carbohydrates, lipids, pentose phosphate, amino acids, nucleotides, and tricarboxylic acid cycle. In the liver, 91% of metabolites displayed rhythmicity with ED + E, whereas in the serum, only 87% were rhythmic. Bioinformatics analysis identified unique metabolome patterns altered in WT CD + M, WT ED + E, Shp-/- CD + M, and Shp-/- ED + E groups. Specifically, metabolites from the nucleotide and amino acid pathway (ribose, glucose-6-phosphate, glutamic acid, aspartic acid, and sedoheptulose-7-P) were elevated in Shp-/- CD + M mice during the dark cycle, whereas metabolites including N-methylalanine, 2-hydroxybutyric acid, and 2-hydroxyglutarate were elevated in WT ED + E mice during the light cycle. The rhythmicity and abundance of other individual metabolites were also significantly altered by both control and EtOH diets.\u0000\u0000\u0000CONCLUSIONS\u0000Metabolomics provides a useful means to identify unique metabolites altered by chronic EtOH-plus-binge.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"39 1","pages":"2548-2556"},"PeriodicalIF":3.2,"publicationDate":"2016-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87091043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice. 免疫球蛋白A基因缺失不影响小鼠酒精性脂肪性肝炎的发生。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-10-14 DOI: 10.1111/acer.13239

Tatsuo Inamine, An-Ming Yang, Lirui Wang, Kuei-Chuan Lee, C. Llorente, B. Schnabl

{"title":"Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice.","authors":"Tatsuo Inamine, An-Ming Yang, Lirui Wang, Kuei-Chuan Lee, C. Llorente, B. Schnabl","doi":"10.1111/acer.13239","DOIUrl":"https://doi.org/10.1111/acer.13239","url":null,"abstract":"BACKGROUND\u0000Chronic alcohol abuse is associated with intestinal dysbiosis and bacterial translocation. Translocated commensal bacteria contribute to alcoholic liver disease. Secretory immunoglobulin A (IgA) in the intestine binds bacteria and prevents bacterial translocation.\u0000\u0000\u0000METHODS\u0000To investigate the functional role of IgA in ethanol (EtOH)-induced liver disease in mice, we subjected wild type (WT) and IgA-deficient littermate mice to Lieber-DeCarli models of chronic EtOH administration and the model of chronic and binge EtOH feeding (the NIAAA model).\u0000\u0000\u0000RESULTS\u0000Chronic EtOH feeding increased systemic levels of IgA, while fecal IgA was reduced in C57BL/6 WT mice. WT and Iga-/- littermate mice showed similar liver injury, steatosis, and inflammation following 4 weeks of EtOH feeding or chronic and binge EtOH feeding. IgA deficiency did not affect intestinal absorption or hepatic metabolism of EtOH. Pretreatment with ampicillin elevated intestinal IgA in WT littermate mice. Despite increased intestinal IgA, WT littermate mice exhibited a similar degree of liver disease compared with Iga-/- mice after 7 weeks of EtOH feeding. Interestingly, bacterial translocation to mesenteric lymph nodes was increased in Iga-/- mice fed an isocaloric diet, but was the same after EtOH feeding relative to WT littermate mice. The absence of intestinal IgA was associated with increased intestinal and plasma IgM in Iga-/- mice after EtOH feeding.\u0000\u0000\u0000CONCLUSIONS\u0000Our findings indicate that absence of IgA does not affect the development of alcoholic liver disease in mice. Loss of intestinal IgA is compensated by increased levels of intestinal IgM, which likely limits bacterial translocation after chronic EtOH administration.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"55 1","pages":"2604-2613"},"PeriodicalIF":3.2,"publicationDate":"2016-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76413495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Nociceptin Receptor as a Target to Treat Alcohol Use Disorder: Challenges in Advancing Medications Development. 痛觉肽受体作为治疗酒精使用障碍的靶点:推进药物开发的挑战

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-10-01 DOI: 10.1111/acer.13222

R. Litten

引用次数: 3

Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior Colliculus. 戒酒增加大鼠下丘蛋白激酶A活性。

IF 3.2 3区医学

Alcoholism, clinical and experimental research Pub Date : 2016-09-26 DOI: 10.1111/acer.13223

Luli R. Akinfiresoye, Clive Miranda, D. Lovinger, P. N'Gouemo

{"title":"Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior Colliculus.","authors":"Luli R. Akinfiresoye, Clive Miranda, D. Lovinger, P. N'Gouemo","doi":"10.1111/acer.13223","DOIUrl":"https://doi.org/10.1111/acer.13223","url":null,"abstract":"BACKGROUND\u0000Cyclic AMP-dependent protein kinase A (PKA) signaling is a key target for the action of alcohol and may therefore play a role in the pathophysiology of alcohol withdrawal seizures (AWSs). Here, we investigated the role of PKA activity with respect to increased seizure susceptibility in rats that were subjected to alcohol withdrawal.\u0000\u0000\u0000METHODS\u0000Adult male Sprague Dawley rats received 3 daily doses of ethanol (EtOH) (or vehicle) for 4 consecutive days. Rats were then tested for susceptibility to acoustically evoked AWSs 3, 24, and 48 hours after the last alcohol dose. In separate experiments, the inferior colliculus (IC) was collected at these same time points from rats subjected to alcohol withdrawal and control rats following alcohol withdrawal. PKA activity, catalytic Cα (PKACα ) protein, regulatory RIIα (PKARIIα ) protein, and RIIβ (PKARIIβ ) protein were measured in the IC. Lastly, in situ pharmacological studies were performed to evaluate whether inhibiting PKA activity in the IC suppressed AWSs.\u0000\u0000\u0000RESULTS\u0000In the EtOH-treated group, AWSs were observed at the 24-hour time point, but not at the 3-hour or 48-hour time points. In the IC, PKA activity was significantly higher both 3 hours (i.e., before AWS susceptibility) and 24 hours after the last alcohol dose (when AWS susceptibility peaked) than in control rats. Consistent with these findings, protein levels of the PKACα subunit were significantly increased in the IC both 3 and 24 hours after the last alcohol dose. Lastly, in situ inhibition of PKA activity within the IC suppressed AWSs.\u0000\u0000\u0000CONCLUSIONS\u0000The increase in PKA activity and PKACα protein expression in the IC preceded the occurrence of AWSs, and inhibiting PKA activity within the IC suppressed acoustically evoked AWSs. Together, these findings suggest that altered PKA activity plays a key role in the pathogenesis of AWSs.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"8 1","pages":"2359-2367"},"PeriodicalIF":3.2,"publicationDate":"2016-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83495761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6