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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 ( IF 5.1 ) Pub Date : 2019-02-28 , DOI: 10.1038/s41434-019-0064-9
Yedy Israel 1 , María Elena Quintanilla 1 , Fernando Ezquer 2 , Paola Morales 1, 3 , Mario Rivera-Meza 4 , Eduardo Karahanian 5 , Marcelo Ezquer 2 , Mario Herrera-Marschitz 1
Affiliation  

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.

中文翻译:

在酒精中毒模型中对获得性和复发性狂饮的基因和细胞疗法:翻译选择。

综述的研究表明,针对抑制由乙醇产生的脑乙醛的合成或降解脑乙醛的慢病毒基因疗法,完全可以阻止因高酒精偏好而饲养的大鼠摄入乙醇。然而,在动物长期饮酒后,上述基因疗法并未抑制酒精的摄入,这表明在慢性乙醇摄入条件下,脑乙醛不再是产生持续酒精增强的化合物。长期摄入乙醇会产生氧化应激和神经炎症,这与长期饮酒和酒精复发“暴饮暴食”密切相关。间充质干细胞,被称为炎症的守护者,释放抗炎细胞因子和抗氧化剂产品。人间充质干细胞的静脉内递送或经鼻内给药的间充质干细胞生成的外泌体既可以逆转(i)酒精诱导的神经炎症和(ii)氧化应激,又可以极大地(iii)抑制(80-90%)慢性饮酒和复发性狂饮。间充质干细胞的治疗作用由脑GLT-1谷氨酸转运蛋白水平的升高介导,表明谷氨酸信号对于酒精复发至关重要。人间充质干细胞和由这些细胞释放的产物在治疗酒精滥用疾病中可能具有翻译价值。(iii)抑制(80-90%)慢性酒精摄入和复发性狂饮。间充质干细胞的治疗作用由脑GLT-1谷氨酸转运蛋白水平的升高介导,表明谷氨酸信号对于酒精复发至关重要。人间充质干细胞和由这些细胞释放的产物可能在酒精滥用疾病的治疗中具有翻译价值。(iii)抑制(80-90%)慢性酒精摄入和复发性狂饮。间充质干细胞的治疗作用由脑GLT-1谷氨酸转运蛋白水平的升高介导,表明谷氨酸信号对于酒精复发至关重要。人间充质干细胞和由这些细胞释放的产物在治疗酒精滥用疾病中可能具有翻译价值。
更新日期:2019-11-18
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