Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options
| dc.contributor.author | Quintanilla, María Elena | |
| dc.contributor.author | Ezquer, Fernando | |
| dc.contributor.author | Morales, Paola | |
| dc.contributor.author | Santapau, Daniela | |
| dc.contributor.author | Berríos-Cárcamo, Pablo | |
| dc.contributor.author | Ezquer, Marcelo | |
| dc.contributor.author | Herrera-Marschitz, Mario | |
| dc.contributor.author | Israel, Yedy | |
| dc.date.accessioned | 2020-04-03T13:58:58Z | |
| dc.date.available | 2020-04-03T13:58:58Z | |
| dc.date.issued | 2019 | |
| dc.description.abstract | Background: Chronic consumption of most drugs of abuse leads to brain oxidative stress and neuroinflammation, which inhibit the glutamate transporter GLT-1, proposed to perpetuate drug intake. The present study aimed at inhibiting chronic ethanol and nicotine self-administration and relapse by the non-invasive intranasal administration of antioxidant and anti-inflammatory secretome generated by adipose tissue-derived activated mesenchymal stem cells. The anti-addiction mechanism of stem cell secretome is also addressed. Methods: Rats bred for their alcohol preference ingested alcohol chronically or were trained to self-administer nicotine. Secretome of human adipose tissue-derived activated mesenchymal stem cells was administered intranasally to animals, both (i) chronically consuming alcohol or nicotine and (ii) during a protracted deprivation before a drug re-access leading to relapse intake. Results: The intranasal administration of secretome derived from activated mesenchymal stem cells inhibited chronic self-administration of ethanol or nicotine by 85% and 75%, respectively. Secretome administration further inhibited by 85–90% the relapse “binge” intake that occurs after a protracted drug deprivation followed by a 60-min drug re-access. Secretome administration fully abolished the oxidative stress induced by chronic ethanol or nicotine self-administration, shown by the normalization of the hippocampal oxidized/reduced glutathione ratio, and the neuroinflammation determined by astrocyte and microglial immunofluorescence. Knockdown of the glutamate transporter GLT-1 by the intracerebral administration of an antisense oligonucleotide fully abolished the inhibitory effect of the secretome on ethanol and nicotine intake. Conclusions: The non-invasive intranasal administration of secretome generated by human adipose tissue-derived activated mesenchymal stem cells markedly inhibits alcohol and nicotine self-administration, an effect mediated by the glutamate GLT-1 transporter. Translational implications are envisioned. | |
| dc.format.extent | 16 p. | |
| dc.identifier.citation | Journal of Stem Cell Research & Therapy. 2019 Jul 8;10(1):205 | |
| dc.identifier.uri | http://hdl.handle.net/11447/3212 | |
| dc.identifier.uri | https://doi.org/10.1186/s13287-019-1304-z | |
| dc.language.iso | en | |
| dc.subject | ROS | |
| dc.subject | Neuroinflammation | |
| dc.subject | Knockdown | |
| dc.subject | GLT-1 antisense | |
| dc.subject | Intranasal | |
| dc.subject | Mesenchymal stem cells | |
| dc.title | Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options | |
| dc.type | Article |