Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats

dc.contributor.authorEzquer, Fernando
dc.contributor.authorQuintanilla, Maria
dc.contributor.authorMorales, Paola
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorLespay, Carolyne
dc.contributor.authorHerrera, Mario
dc.contributor.authorIsrael, Yedy
dc.date.accessioned2018-01-09T17:40:01Z
dc.date.available2018-01-09T17:40:01Z
dc.date.issued2017
dc.description.abstractNeuroinflammation has been reported to follow chronic ethanol intake and may perpetuate alcohol consumption. Present studies determined the effect of human mesenchymal stem cells (hMSCs), known for their anti-inflammatory action, on chronic ethanol intake and relapse-like ethanol intake in a post-deprivation condition. Rats were allowed 12-17 weeks of chronic voluntary ethanol (10% and 20% v/v) intake, after which a single dose of activated hMSCs (5 × 105 ) was injected into a brain lateral ventricle. Control animals were administered vehicle. After assessing the effect of hMSCs on chronic ethanol intake for 1 week, animals were deprived of ethanol for 2 weeks and thereafter an ethanol re-access of 60 min was allowed to determine relapse-like intake. A single administration of activated hMSCs inhibited chronic alcohol consumption by 70% (P < 0.001), an effect seen within the first 24 hours of hMSCs administration, and reduced relapse-like drinking by 80% (P < 0.001). In the relapse-like condition, control animals attain blood ethanol ('binge-like') levels >80 mg/dl. The single hMSC administration reduced relapse-like blood ethanol levels to 20 mg/dl. Chronic ethanol intake increased by 250% (P < 0.001) the levels of reactive oxygen species in hippocampus, which were markedly reduced by hMSC administration. Astrocyte glial acidic fibrillary protein immunoreactivity, a hallmark of neuroinflammation, was increased by 60-80% (P < 0.001) by chronic ethanol intake, an effect that was fully abolished by the administration of hMSCs. This study supports the neuroinflammation-chronic ethanol intake hypothesis and suggest that mesenchymal stem cell administration may be considered in the treatment of alcohol use disorders.
dc.description.versionVersión Publicada
dc.format.extent11
dc.identifier.citationEzquer F, Quintanilla ME, Morales P, Ezquer M, Lespay-Rebolledo C, Herrera-Marschitz M, Israel Y. Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats. Addict Biol. 2019 Jan;24(1):17-27. doi: 10.1111/adb.12572.
dc.identifier.urihttp://hdl.handle.net/11447/1867
dc.identifier.urihttp://dx.doi.org/10.1111/adb.12572
dc.language.isoen_US
dc.publisherJohn Wiley & Sons
dc.sourceAddiction Biology
dc.subjectGFAP
dc.subjectLPS
dc.subjectTNF-alpha
dc.subjectalcohol preferring rats
dc.subjectalcoholism
dc.subjectbinge drinking
dc.subjectglutathione
dc.subjectoxidative stress
dc.titleActivated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats
dc.typeArtículo

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