Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking.

dc.contributor.authorEzquer, Fernando
dc.contributor.authorQuintanilla, María Elena
dc.contributor.authorMorales, Paola
dc.contributor.authorSantapau, Daniela
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorKogan, Marcelo J.
dc.contributor.authorSalas-Huenuleo, Edison
dc.contributor.authorHerrera-Marschitz, Mario
dc.contributor.authorIsrael, Yedy
dc.date.accessioned2020-04-03T14:54:30Z
dc.date.available2020-04-03T14:54:30Z
dc.date.issued2019
dc.description.abstractChronic ethanol consumption leads to brain oxidative stress and neuroinflammation, conditions known to potentiate and perpetuate each other. Several studies have shown that neuroinflammation results in increases in chronic ethanol consumption. Recent reports showed that the intra-cerebroventricular administration of mesenchymal stem cells to rats consuming alcohol chronically markedly inhibited oxidative-stress, abolished neuroinflammation and greatly reduced chronic alcohol intake and post deprivation relapselike alcohol intake. However, the intra-cerebroventricular administration of living cells is not suitable as a treatment of a chronic condition. The present study aimed at inhibiting ethanol intake by the noninvasive intranasal administration of human mesenchymal stem cell products: exosomes; microvesicles (40 to 150 nm) with marked antioxidant activity extruded from mesenchymal stem cells. The exosome membrane can fuse with the plasma membrane of cells in different tissues, thus delivering their content intracellularly. The study showed that the weekly intranasal administration of mesenchymal stem cell-derived exosomes to rats consuming alcohol chronically (i) inhibited their ethanol intake by 80% and blunted the relapselike “binge” drinking that follows an alcohol deprivation period and ethanol re-access. (ii) Intranasally administered exosomes were found in the brain within 24-hours; (iii) fully reversed both alcohol-induced hippocampal oxidative-stress, evidenced by a lower ratio of oxidized to reduced glutathione, and neuroinflammation, shown by a reduced astrocyte activation and microglial density and (iv) increased glutamate transporter GLT1 expression in nucleus accumbens, counteracting the inhibition of glutamate transporter activity, reportedly depressed under oxidative-stress conditions. Possible translational implications are envisaged
dc.description.versionVersión enviada
dc.format.extent50 p.
dc.identifier.citationEzquer F, Quintanilla ME, Morales P, Santapau D, Ezquer M, Kogan MJ, Salas-Huenuleo E, Herrera-Marschitz M, Israel Y. Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking. Addict Biol. 2019 Sep;24(5):994-1007. doi: 10.1111/adb.12675.
dc.identifier.urihttp://hdl.handle.net/11447/3214
dc.identifier.urihttps://doi.org/10.1111/adb.12675
dc.language.isoen
dc.sourceAddiction Biology
dc.subjectADE
dc.subjectGLT-1
dc.subjectNoninvasive
dc.subjectBinge-drinking
dc.subjectMesenchymal stem cells
dc.subjectExosomes
dc.titleIntranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking.
dc.typeArticle

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