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Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options

Gene Therapy volume 26, pages 407–417 (2019)Cite this article

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Abstract

Studies reviewed show that lentiviral gene therapy directed either at inhibiting the synthesis of brain acetaldehyde generated from ethanol or at degrading brain acetaldehyde fully prevent ethanol intake by rats bred for their high alcohol preference. However, after animals have chronically consumed alcohol, the above gene therapy did not inhibit alcohol intake, indicating that in the chronic ethanol intake condition brain acetaldehyde is no longer the compound that generates the continued alcohol reinforcement. Oxidative stress and neuroinflammation generated by chronic ethanol intake are strongly associated with the perpetuation of alcohol consumption and alcohol relapse “binge drinking”. Mesenchymal stem cells, referred to as guardians of inflammation, release anti-inflammatory cytokines and antioxidant products. The intravenous delivery of human mesenchymal stem cells or the intranasal administration of mesenchymal stem cell-generated exosomes reverses both (i) alcohol-induced neuro-inflammation and (ii) oxidative stress, and greatly (iii) inhibits (80–90%) chronic alcohol intake and relapse binge-drinking. The therapeutic effect of mesenchymal stem cells is mediated by increased levels of the brain GLT-1 glutamate transporter, indicating that glutamate signaling is pivotal for alcohol relapse. Human mesenchymal stem cells and the products released by these cells may have translational value in the treatment of alcohol-use disorders.

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Acknowledgements

Studies presented were supported by NIAAA R01AA 10630, ICM-P99-03, Fondecyt #1080447, #1095021; #1130012, #1150589, #1170712, and #1180042 (Chile).

Author contributions

YI and MEQ drafted the review and all authors contributed to improving the text and approved the final manuscript.

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Author notes

  1. These authors contributed equally: Yedy Israel, María Elena Quintanilla

Authors and Affiliations

  1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile

    Yedy Israel, María Elena Quintanilla, Paola Morales & Mario Herrera-Marschitz

  2. Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago, Chile

    Fernando Ezquer & Marcelo Ezquer

  3. Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile

    Paola Morales

  4. Department of Pharmacological and Toxicological Chemistry, Faculty of Chemical Sciences and Pharmacy, University of Chile, Santiago, Chile

    Mario Rivera-Meza

  5. Institute of Biomedical Sciences, Universidad Autónoma de Chile, Santiago, Chile

    Eduardo Karahanian

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Yedy Israel, Quintanilla, M.E., Ezquer, F. et al. Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options. Gene Ther 26, 407–417 (2019). https://doi.org/10.1038/s41434-019-0064-9

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