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BIOL PSYCHIAT:Nf1基因突变与酒精依赖风险相关

2014-09-04 万纹 生物通

科学家们之前曾发现1型神经纤维瘤(NF1)基因与酒精依赖性有关,这种作用可能是通过调节γ-氨基丁酸(γ-GABA)来实现对酒精摄入的影响。最近的一篇文章,来自Scripps研究所的研究人员则发现γ-氨基丁酸这种神经递质能降低焦虑情绪,促进情绪的放松,研究人员指出这一发现将人体Nf1基因的突变,与酒精依赖性风险及严重程度联系在了一起。 这一研究成果公布在8月18日 Biologi

科学家们之前曾发现1型神经纤维瘤NF1)基因与酒精依赖性有关,这种作用可能是通过调节γ-氨基丁酸(γ-GABA)来实现对酒精摄入的影响。最近的一篇文章,来自Scripps研究所的研究人员则发现γ-氨基丁酸这种神经递质能降低焦虑情绪,促进情绪的放松,研究人员指出这一发现将人体Nf1基因的突变,与酒精依赖性风险及严重程度联系在了一起。

这一研究成果公布在8月18日 Biological Psychiatry杂志上。

文章作者之一,Vez Repunte-Canonigo表示,“尽管研究表明酒精上瘾与遗传因素关系极大,但是目前发现的相关风险基因很少,而且这些基因的作用机制也模糊不清。”

这一研究小组希望能找到神经递质GABA的作用关联,之前的研究发现这种细胞因子是在中央杏仁核中被释放,这是大脑中参与决策、压力和成瘾的一个区域。

“(这一区域)对从小饮小酌发展到酒精成瘾至关重要,”文章作者,Melissa Herman说。

研究人员分析了酒精成瘾的小鼠模型,结果发现携带功能性Nf1基因的小鼠在单周期饮酒后增加其酒精耐受性,但被敲除一个基因拷贝的小鼠则不能增加酒精耐受性。而且对于杂合Nf1小鼠来说,摄入酒精不会导致中央杏仁核中GABA释放量的增加,但带有两个功能性拷贝的小鼠则会增加GABA释放量。

此外,研究人员还利用来自9000人的数据分析人体Nf1基因突变,他们发现这一基因与酒精依赖性和严重程度有关。“更好的理解酒精依赖发生过程中的分子机制,将有助于研发预防和治疗酒精依赖性的新方法,”文章作者Pietro Paolo Sanna 说。

今年还有研究组发现了“千杯不醉”基因:美国德克萨斯大学奥斯汀分校的科学家通过向蠕虫注射一种能够抵消酒精麻痹作用的新成分,成功将普通蠕虫变成“千杯不醉”。

研究人员通过基因修饰来修改其体内的一个靶蛋白。靶蛋白是生物体大脑感知酒精的分子通道(BK通道)。他们将该蠕虫放入酒精的培养皿中,它很快会醉倒,表现为爬行缓慢,尾巴摇摆次数变少,但是经过基因改造后,这条虫子在培养皿中完全没有喝醉的迹象,还是依旧活跃。

研究者表示,人们之所以会醉酒是因为酒精会对神经元中掌管活跃度、呼吸、血流和膀胱系统调节的BK通道产生影响,从而让人体失去正常的活动功能。而这项发现的新成分可以让BK通道正常工作,同时抵消酒精的副作用。

原始出处:

Nf1 regulates alcohol dependence-associated excessive drinking and GABA release in the central amygdala in mice, and is associated with alcohol dependence in humans

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    2015-07-24 ay2000fy
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    2015-07-25 sunylz
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