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description Publicationkeyboard_double_arrow_right Article , Other literature type 2023Publisher:Springer Science and Business Media LLC Funded by:NIH | Role of BK Channel Intera..., NIH | Activation of the parasub..., NIH | CORE--BIOCHEMICAL CORENIH| Role of BK Channel Interactome in Excessive Ethanol Drinking ,NIH| Activation of the parasubthalamic nucleus in alcohol dependence ,NIH| CORE--BIOCHEMICAL COREAuthors: Agbonlahor Okhuarobo; Max Kreifeldt;Pauravi J. Gandhi;
Catherine Lopez; +9 AuthorsPauravi J. Gandhi
Pauravi J. Gandhi in OpenAIREAgbonlahor Okhuarobo; Max Kreifeldt;Pauravi J. Gandhi;
Catherine Lopez; Briana Martinez;Pauravi J. Gandhi
Pauravi J. Gandhi in OpenAIREKiera Fleck;
Michal Bajo;Kiera Fleck
Kiera Fleck in OpenAIREPushpita Bhattacharyya;
Alex M. Dopico;Pushpita Bhattacharyya
Pushpita Bhattacharyya in OpenAIREMarisa Roberto;
Amanda J. Roberts;Marisa Roberto
Marisa Roberto in OpenAIREGregg E. Homanics;
Gregg E. Homanics
Gregg E. Homanics in OpenAIRECandice Contet;
Candice Contet
Candice Contet in OpenAIREAbstractLarge conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol and genetic variations in the channel-forming α subunit have been nominally associated with alcohol use disorders. However, whether the action of ethanol at BK α influences the motivation to drink alcohol remains to be determined. To address this question, we first tested the effect of systemically administered BK channel modulators on voluntary alcohol consumption in C57BL/6J males. Penitrem A (blocker) exerted dose-dependent effects on moderate alcohol intake, while paxilline (blocker) and BMS-204352 (opener) were ineffective. Because pharmacological manipulations are inherently limited by non-specific effects, we then sought to investigate the behavioral relevance of ethanol’s direct interaction with BK α by introducing in the mouse genome a point mutation known to render BK channels insensitive to ethanol while preserving their physiological function. The BK α K361N substitution prevented ethanol from reducing spike threshold in medial habenula neurons. However, it did not alter acute responses to ethanol in vivo, including ataxia, sedation, hypothermia, analgesia, and conditioned place preference. Furthermore, the mutation did not have reproducible effects on alcohol consumption in limited, continuous, or intermittent access home cage two-bottle choice paradigms conducted in both males and females. Notably, in contrast to previous observations made in mice missing BK channel auxiliary β subunits, the BK α K361N substitution had no significant impact on ethanol intake escalation induced by chronic intermittent alcohol vapor inhalation. It also did not affect the metabolic and locomotor consequences of chronic alcohol exposure. Altogether, these data suggest that the direct interaction of ethanol with BK α does not mediate the alcohol-related phenotypes examined here in mice.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41380-023-02346-y&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 2 citations 2 popularity Average influence Average impulse Average Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41380-023-02346-y&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2009Publisher:Wiley Authors: Rueben A. Gonzales; Scott McConnell;Donita L. Robinson;
Donita L. Robinson; +2 AuthorsDonita L. Robinson
Donita L. Robinson in OpenAIRERueben A. Gonzales; Scott McConnell;Donita L. Robinson;
Donita L. Robinson; Elaina C. Howard; R. Mark Wightman;Donita L. Robinson
Donita L. Robinson in OpenAIREBackground: Dopamine concentrations in the nucleus accumbens fluctuate on phasic (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol increases tonic concentrations of dopamine, but its effect on subsecond dopamine transients has not been fully explored.Methods: We measured tonic and phasic dopamine fluctuations in the nucleus accumbens of rats in response to ethanol (within‐subject cumulative dosing, 0.125 to 2 g/kg, i.v.).Results: Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between‐site effects reflected specific pharmacology at that recording site.Conclusions: These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens.
Alcoholism Clinical ... arrow_drop_down Alcoholism Clinical and Experimental ResearchArticle . 2009 . Peer-reviewedLicense: Wiley Online Library User AgreementData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1111/j.1530-0277.2009.00942.x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 86 citations 86 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!
more_vert Alcoholism Clinical ... arrow_drop_down Alcoholism Clinical and Experimental ResearchArticle . 2009 . Peer-reviewedLicense: Wiley Online Library User AgreementData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1111/j.1530-0277.2009.00942.x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023Embargo end date: 01 Aug 2024 GermanyPublisher:Wiley Funded by:EC | NovAnI, NWO | New concepts in catalytic...EC| NovAnI ,NWO| New concepts in catalytic lignin depolymerization: sustainable pathways towards value added chemicalsAuthors:Anastasiia M. Afanasenko;
Xianyuan Wu;Anastasiia M. Afanasenko
Anastasiia M. Afanasenko in OpenAIREAlessandra De Santi;
Alessandra De Santi
Alessandra De Santi in OpenAIREWalid A. M. Elgaher;
+7 AuthorsWalid A. M. Elgaher
Walid A. M. Elgaher in OpenAIREAnastasiia M. Afanasenko;
Xianyuan Wu;Anastasiia M. Afanasenko
Anastasiia M. Afanasenko in OpenAIREAlessandra De Santi;
Alessandra De Santi
Alessandra De Santi in OpenAIREWalid A. M. Elgaher;
Andreas M. Kany; Roya Shafiei; Marie‐Sophie Schulze; Thomas F. Schulz;Walid A. M. Elgaher
Walid A. M. Elgaher in OpenAIREJörg Haupenthal;
Jörg Haupenthal
Jörg Haupenthal in OpenAIREAnna K. H. Hirsch;
Anna K. H. Hirsch
Anna K. H. Hirsch in OpenAIREKatalin Barta;
Katalin Barta
Katalin Barta in OpenAIREAbstractDeriving active pharmaceutical agents from renewable resources is crucial to increasing the economic feasibility of modern biorefineries and promises to alleviate critical supply‐chain dependencies in pharma manufacturing. Our multidisciplinary approach combines research in lignin‐first biorefining, sustainable catalysis, and alternative solvents with bioactivity screening, an in vivo efficacy study, and a structural‐similarity search. The resulting sustainable path to novel anti‐infective, anti‐inflammatory, and anticancer molecules enabled the rapid identification of frontrunners for key therapeutic indications, including an anti‐infective against the priority pathogen Streptococcus pneumoniae with efficacy in vivo and promising plasma and metabolic stability. Our catalytic methods provided straightforward access, inspired by the innate structural features of lignin, to synthetically challenging biologically active molecules with the core structure of dopamine, namely, tetrahydroisoquinolines, quinazolinones, 3‐arylindoles and the natural product tetrahydropapaveroline. Our diverse array of atom‐economic transformations produces only harmless side products and uses benign reaction media, such as tunable deep eutectic solvents for modulating reactivity in challenging cyclization steps.
Angewandte Chemie arrow_drop_down Angewandte Chemie International EditionArticle . 2023 . Peer-reviewedLicense: CC BYData sources: CrossrefAngewandte Chemie International EditionArticle . 2023License: CC BYData sources: University of Groningen Research PortalScientific documents from the Saarland UniversityArticle . 2024License: CC BYData sources: Scientific documents from the Saarland Universityadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1002/ange.202308131&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu15 citations 15 popularity Average influence Average impulse Top 10% Powered by BIP!
more_vert Angewandte Chemie arrow_drop_down Angewandte Chemie International EditionArticle . 2023 . Peer-reviewedLicense: CC BYData sources: CrossrefAngewandte Chemie International EditionArticle . 2023License: CC BYData sources: University of Groningen Research PortalScientific documents from the Saarland UniversityArticle . 2024License: CC BYData sources: Scientific documents from the Saarland Universityadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1002/ange.202308131&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2015Publisher:Ovid Technologies (Wolters Kluwer Health) Authors:Changya Peng;
José A. Rafols; Huishan Du; Xunming Ji; +5 AuthorsChangya Peng
Changya Peng in OpenAIREChangya Peng;
José A. Rafols; Huishan Du; Xunming Ji;Changya Peng
Changya Peng in OpenAIREXiaokun Geng;
Omar Elmadhoun; Adam Hafeez; Zongjian Liu; Yuchuan Ding;Xiaokun Geng
Xiaokun Geng in OpenAIREpmid: 25563647
Background and Purpose— Ischemic stroke induces metabolic disarray. A central regulatory site, pyruvate dehydrogeanse complex (PDHC) sits at the cross-roads of 2 fundamental metabolic pathways: aerobic and anaerobic. In this study, we combined ethanol (EtOH) and normobaric oxygen (NBO) to develop a novel treatment to modulate PDHC and its regulatory proteins, namely pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase, leading to improved metabolism and reduced oxidative damage. Methods— Sprague–Dawley rats were subjected to transient (2, 3, or 4 hours) middle cerebral artery occlusion followed by 3- or 24-hour reperfusion, or permanent (28 hours) middle cerebral artery occlusion without reperfusion. At 2 hours after the onset of ischemia, rats received either an intraperitoneal injection of saline, 1 dose of EtOH (1.5 g/kg) for 2- and 3-hour middle cerebral artery occlusion, 2 doses of EtOH (1.5 g/kg followed by 1.0 g/kg in 2 hours) in 4 hours or permanent middle cerebral artery occlusion, and EtOH+95% NBO (at 2 hours after the onset of ischemia for 6 hours) in permanent stroke. Infarct volumes and neurological deficits were examined. Oxidative metabolism and stress were determined by measuring ADP/ATP ratio and reactive oxygen species levels. Protein levels of PDHC, pyruvate dehydrogenase kinase, and pyruvate dehydrogenase phosphatase were assessed. Results— EtOH induced dose-dependent neuroprotection in transient ischemia. Compared to EtOH or NBO alone, NBO+EtOH produced the best outcomes in permanent ischemia. These therapies improved brain oxidative metabolism by decreasing ADP/ATP ratios and reactive oxygen species levels, in association with significantly raised levels of PDHC and pyruvate dehydrogenase phosphatase, as well as decreased pyruvate dehydrogenase kinase. Conclusions— Both EtOH and EtOH+NBO treatments conferred neuroprotection in severe stroke by affecting brain metabolism. The treatment may modulate the damaging cascade of metabolic events by bringing the PDHC activity back to normal metabolic levels.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1161/strokeaha.114.006994&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 37 citations 37 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1161/strokeaha.114.006994&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2004Publisher:Wiley Authors: Tamara J. Phillips;Helen M. Kamens;
John C. Crabbe;Helen M. Kamens
Helen M. Kamens in OpenAIRESarah E. Holstein;
Sarah E. Holstein
Sarah E. Holstein in OpenAIREpmid: 15924557
Impairment of motor coordination, or ataxia, is a prominent effect of alcohol ingestion in humans. To date, many models have been created to examine this phenomenon in animals. Evidence suggests that the tasks thought to measure this behavior in mice actually measure different components of this complex trait. We have characterized the parallel rod floor apparatus to quantify ethanol‐induced motor incoordination. Using genetically heterogeneous mice, we evaluated the influence of rod diameter and inter‐rod distance on dose‐related ethanol‐induced motor incoordination to select parameters that optimized testing procedures. We then used the DBA/2J and C57BL/6J inbred strains of mice to examine the effect of 2 g/kg of ethanol, by serially testing mice on two floor types, separated by 1 week. Finally, we tested eight inbred strains of mice on four floor types to examine patterns of strain sensitivity to 2 g/kg of intraperitoneal ethanol and determined the test parameters that maximized strain effect size. Motor incoordination varied depending on the floor type and strain. When data from strain 129S1/SvlmJ were removed from the analyses because of their extreme behavior, the greatest strain effect size was observed on one floor type during the first 10 min of testing after 2 g/kg of intraperitoneal ethanol. These findings suggest that the parallel rod floor apparatus provides a useful means for examining ethanol‐induced motor incoordination in mice but that specific testing procedures are important for optimizing detection of motor incoordination and genetic influences.
Genes Brain & Behavi... arrow_drop_down Genes Brain & BehaviorArticle . 2004 . Peer-reviewedLicense: Wiley Online Library User AgreementData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1111/j.1601-183x.2004.00100.x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 25 citations 25 popularity Top 10% influence Average impulse Average Powered by BIP!
more_vert Genes Brain & Behavi... arrow_drop_down Genes Brain & BehaviorArticle . 2004 . Peer-reviewedLicense: Wiley Online Library User AgreementData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1111/j.1601-183x.2004.00100.x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2014Publisher:Informa UK Limited Authors:Monique L. Smith;
Monique L. Smith
Monique L. Smith in OpenAIREAndrey E. Ryabinin;
Allison M.J. Anacker;Andrey E. Ryabinin
Andrey E. Ryabinin in OpenAIREDominance hierarchies are an important aspect of group-living as they determine individual access to resources. The existence of dominance ranks in access to space has not been described in socially monogamous, communally nesting prairie voles (Microtus ochrogaster). Here, we tested whether dominance could be assessed using the tube test. We also tested whether dominance related to alcohol intake, similar to what has been demonstrated in nonmonogamous species. Same-sex pairs of unfamiliar peers were tested in a series of three trials of the tube test, then paired and allowed individual access to alcohol and water for 4 days, and then tested again in the tube test. For all pairs, the same subjects won the majority of trials before and after alcohol drinking. The number of wins negatively correlated with alcohol intake on the first day of drinking and positively correlated with levels of Fos in the paraventricular nucleus of the hypothalamus following the tube test in a separate group of voles. Dominance was not related to Fos levels in other brain regions examined. Together, these results indicate that prairie voles quickly establish stable dominance ranks through a process possibly involving the hypothalamus and suggest that dominance is linked to alcohol drinking.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1080/17470919.2014.931885&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 18 citations 18 popularity Top 10% influence Average impulse Average Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1080/17470919.2014.931885&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2018 AustraliaPublisher:Elsevier BV Funded by:ARC | Discovery Projects - Gran...ARC| Discovery Projects - Grant ID: DP110100297Authors: Jacobsen, J.;Buisman-Pijlman, F.;
Buisman-Pijlman, F.
Buisman-Pijlman, F. in OpenAIREMustafa, S.;
Rice, K.; +1 AuthorsMustafa, S.
Mustafa, S. in OpenAIREJacobsen, J.;Buisman-Pijlman, F.;
Buisman-Pijlman, F.
Buisman-Pijlman, F. in OpenAIREMustafa, S.;
Rice, K.;Mustafa, S.
Mustafa, S. in OpenAIREHutchinson, M.;
Hutchinson, M.
Hutchinson, M. in OpenAIREAdolescents frequently engage in risky behaviours such as binge drinking. Binge drinking, in turn, perturbs neurodevelopment reinforcing reward seeking behaviour in adulthood. Current animal models are limited in their portrayal of this behaviour and the assessment of neuroimmune involvement (specifically the role of Toll-like receptor 4 (TLR4)). Therefore, the aims of this project were to develop a more relevant animal model of adolescent alcohol exposure and to characterise its effects on TLR4 signalling and alcohol-related behaviours later life. Balb/c mice received a short (P22-P25), low dose alcohol binge during in early adolescence, and underwent tests to investigate anxiety (elevated plus maze), alcohol seeking (conditioned place preference) and binge drinking behaviour (drinking in the dark) in adulthood. Four doses of alcohol during adolescence increased alcohol-induced conditioned place preference and alcohol intake in adulthood. However, this model did not affect basal elevated plus maze performance. Subsequent analysis of nucleus accumbal mRNA, revealed increased expression of TLR4-related mRNAs in mice who received alcohol during adolescence. To further elucidate the role of TLR4, (+)-Naltrexone, a biased TLR4 antagonist was administered 30 min before or after the adolescent binge paradigm. When tested in adulthood, (+)-Naltrexone treated mice exhibited reduced alcohol intake however, alcohol seeking and anxiety behaviour was unaltered. This study highlights that even a small amount of alcohol, when given during a critical neurodevelopmental period, can potentiate alcohol-related behaviours and TLR4 activation later in life. Interestingly, attenuation of TLR4 before or after adolescent alcohol exposure reduced only binge alcohol intake in adulthood.
Neuropharmacology arrow_drop_down The University of Adelaide: Digital LibraryArticle . 2018Data sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.neuropharm.2017.09.028&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 14 citations 14 popularity Top 10% influence Average impulse Top 10% Powered by BIP!
more_vert Neuropharmacology arrow_drop_down The University of Adelaide: Digital LibraryArticle . 2018Data sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.neuropharm.2017.09.028&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2017Publisher:Wiley Authors:Jessie Newville;
Carlos Fernando Valenzuela; Lu Li;Jessie Newville
Jessie Newville in OpenAIRELauren L. Jantzie;
+1 AuthorsLauren L. Jantzie
Lauren L. Jantzie in OpenAIREJessie Newville;
Carlos Fernando Valenzuela; Lu Li;Jessie Newville
Jessie Newville in OpenAIRELauren L. Jantzie;
Lee Anna Cunningham;Lauren L. Jantzie
Lauren L. Jantzie in OpenAIREAbstractAlcohol exposure during central nervous system (CNS) development can lead to fetal alcohol spectrum disorder (FASD). Human imaging studies have revealed significant white matter (WM) abnormalities linked to cognitive impairment in children with FASD; however, the underlying mechanisms remain unknown. Here, we evaluated both the acute and long‐term impacts of alcohol exposure on oligodendrocyte number and WM integrity in a third trimester‐equivalent mouse model of FASD, in which mouse pups were exposed to alcohol during the first 2 weeks of postnatal development. Our results demonstrate a 58% decrease in the number of mature oligodendrocytes (OLs) and a 75% decrease in the number of proliferating oligodendrocyte progenitor cells (OPCs) within the corpus callosum of alcohol‐exposed mice at postnatal day 16 (P16). Interestingly, neither mature OLs nor OPCs derived from the postnatal subventricular zone (SVZ) were numerically affected by alcohol exposure, indicating heterogeneity in susceptibility based on OL ontogenetic origin. Although mature OL and proliferating OPC numbers recovered by postnatal day 50 (P50), abnormalities in myelin protein expression and microstructure within the corpus callosum of alcohol‐exposed subjects persisted, as assessed by western immunoblotting of myelin basic protein (MBP; decreased expression) and MRI diffusion tensor imaging (DTI; decreased fractional anisotropy). These results indicate that third trimester‐equivalent alcohol exposure leads to an acute, albeit recoverable, decrease in OL lineage cell numbers, accompanied by enduring WM injury. Additionally, our finding of heterogeneity in alcohol susceptibility based on the developmental origin of OLs may have therapeutic implications in FASD and other disorders of WM development.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1002/glia.23164&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 45 citations 45 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1002/glia.23164&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2016Publisher:Springer Science and Business Media LLC Yu-Lan Zhu; Qun Wang; Anchen Guo; Wei-Wei Li; Fang Su; Yongjun Wang; Yi-Long Zhao; Zhengyi Qu;Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca2+-activated K+ channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BKCa channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+ and preventing neuronal apoptosis, and this is mediated by BKCa channel activation.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1007/s12264-016-0080-3&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 33 citations 33 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1007/s12264-016-0080-3&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Journal 2008 AustraliaPublisher:Elsevier BV Nielsen, Carsten; Simms, Jeffrey; Pierson, Haley; Li, Rui; Saini, Surendra; Ananthan, Subramaniam; Bartlett, Selena;Naltrexone, a compound with high affinity for the mu opioid receptor (MOP-R) reduces alcohol consumption. SoRI-9409 is a derivative of naltrexone that has highest affinity at delta opioid receptors (DOP-Rs). We have investigated the effects of SoRI-9409 on ethanol consumption to determine the consequences of altering the naltrexone compound to a form with increased efficacy at DOP-Rs.Effects of the opioid receptor antagonists, SoRI-9409 (0-30 mg/kg, IP), naltrexone (0-30 mg/kg, IP), or naltrindole (0-10 mg/kg, IP) on ethanol consumption was measured in high- and low-ethanol-consuming rats with two different drinking paradigms. SoRI-9409-, naltrexone-, and naltrindole-mediated inhibition of DOP-R-stimulated [(35)S]GTP gamma S binding was measured in brain membranes prepared from high-ethanol-consuming rats. The effects of SoRI-9409 on morphine-mediated analgesia, conditioned place preference, and anxiety were also examined.In high- but not low-ethanol-consuming animals, SoRI-9409 is threefold more effective and selective at reducing ethanol consumption when compared with naltrexone or naltrindole for up to 24 hours. SoRI-9409 administered daily for 28 days continuously reduced ethanol consumption, and when the administration of SoRI-9409 was terminated, the amount of ethanol consumed remained lower compared with vehicle-treated animals. Furthermore, SoRI-9409 inhibits DOP-R-stimulated [(35)S]GTP gamma S binding in brain membranes of high-ethanol-consuming rats.SoRI-9409 causes selective and long-lasting reductions of ethanol consumption. This suggests that compounds that have high affinity for DOP-Rs such as SoRI-9409 might be promising candidates for development as a novel therapeutic for the treatment of alcoholism.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.biopsych.2008.07.018&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 41 citations 41 popularity Average influence Top 10% impulse Top 10% Powered by BIP!
more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.biopsych.2008.07.018&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu