Artificial microRNA-based neurokinin-1 receptor gene silencing reduces alcohol consumption in mice
Artificial microRNA-based neurokinin-1 receptor gene silencing reduces alcohol consumption in mice
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DOI：
10.1016/j.neulet.2010.03.051
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发表时间：
2010-05-21
影响因子：
2.5
通讯作者：
Chai, Young Gyu
中科院分区：
文献类型：
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作者：
Baek, Mi Na;Jung, Kyoung Hwa;Chai, Young Gyu
在大脑中，压力系统在刺激持续饮酒和复发方面起着重要作用。神经肽物质P和神经激肽-1受体（NK1R）参与应激反应和药物奖励系统。最近的研究结果表明，配体与NK1Rs的结合减少了小鼠对酒精的自我给药。我们研究了人工microRNA （amiRNA）对小鼠大脑中NK1R功能表达的影响。将表达靶向NK1R的amiRNA （amiNK1R）或阴性对照amiRNA （amiNC）的慢病毒注射到小鼠大脑中。在注射amiRNA四周后，我们发现与注射amiNC的小鼠相比，amiNK1R减少了自愿酒精消耗量。我们还观察到海马中NK1R的表达减少。RNA干扰是调控特定行为相关基因表达的有效途径。我们的研究结果支持amiRNA作为酒精依赖治疗药物的潜在用途。2010爱思唯尔爱尔兰有限公司版权所有。
In the brain, the stress system plays an important role in motivating continued alcohol use and relapse. The neuropeptide substance P and the neurokinin-1 receptor (NK1R) are involved in the stress response and drug reward systems. Recent findings have shown that the binding of ligands to NK1Rs decreases the self-administration of alcohol in mice. We examined the effect of an artificial microRNA (amiRNA) on the functional expression of NK1R in mouse brains. Lentiviruses expressing either an amiRNA targeting the NK1R (amiNK1R) or a negative control amiRNA (amiNC) were injected into mouse brains. Four weeks after amiRNA injection, we found that amiNK1R decreased the voluntary alcohol consumption compared to mice injected with amiNC. We also observed that NK1R expression was reduced in the hippocampus. RNA interference is an effective approach to regulate the expression of specific behavior-related genes. Our results support the potential use of amiRNA as a therapeutic agent for the treatment of alcohol dependence. (C) 2010 Elsevier Ireland Ltd. All rights reserved.