Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking.
Date
2019
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Article
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50 p.
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Abstract
Chronic 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
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Citation
Ezquer 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.
Keywords
ADE, GLT-1, Noninvasive, Binge-drinking, Mesenchymal stem cells, Exosomes