A role for repressive histone methylation in cocaine-induced vulnerability to stress.
A role for repressive histone methylation in cocaine-induced vulnerability to stress.
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DOI：
10.1016/j.neuron.2011.06.007
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发表时间：
2011-08-25
期刊：
影响因子：
16.2
通讯作者：
Nestler EJ
中科院分区：
文献类型：
--
作者：
Covington HE 3rd;Maze I;Sun H;Bomze HM;DeMaio KD;Wu EY;Dietz DM;Lobo MK;Ghose S;Mouzon E;Neve RL;Tamminga CA;Nestler EJ
药物滥用增加了一个人对与压力有关的疾病的脆弱性，这可能是由药物引起的神经适应性改变随后对压力的反应介导的。在这里，我们确定了抑制性组蛋白甲基化的核神经元（NAc），一个重要的大脑奖励区域，作为一个关键的机制连接可卡因暴露增加的压力脆弱性。在慢性社会失败应激之前重复给予可卡因通过降低NAc中组蛋白H3赖氨酸9二甲基化水平增强小鼠的抑郁样行为。铬介导的组蛋白甲基转移酶，G9 a，在NAc的减少促进社会压力的易感性增加，类似于观察到的重复可卡因。相反，重复可卡因后NAc中的G9 a过表达保护小鼠免受随后应激的后果。这种弹性部分是通过抑制BDNF-TrkB-CREB信号传导介导的，这是在重复可卡因或压力后诱导的。确定这些共同的调节机制可能有助于开发成瘾和抑郁症的新疗法。
Substance abuse increases an individual's vulnerability to stress-related illnesses, which is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress. Here, we identify repressive histone methylation in nucleus accumbens (NAc), an important brain reward region, as a key mechanism linking cocaine exposure to increased stress vulnerability. Repeated cocaine administration prior to chronic social defeat stress potentiated depressive-like behaviors in mice through decreased levels of histone H3 lysine 9 dimethylation in NAc. Cre-mediated reduction of the histone methyltransferase, G9a, in NAc promoted increased susceptibility to social stress, similar to that observed with repeated cocaine. Conversely, G9a overexpression in NAc after repeated cocaine protected mice from the consequences of subsequent stress. This resilience was mediated, in part, through repression of BDNF-TrkB-CREB signaling, which was induced after repeated cocaine or stress. Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression.
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DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
--
作者：
Akbarian, S;Ruehl, MG;Guo, Y
通讯作者：
Guo, Y
影响因子：
7.6
作者：
Covington, HE;Kikusui, T;Miczek, KA
通讯作者：
Miczek, KA
影响因子：
7.6
作者：
Ferguson, Susan M.;Fasano, Stefania;Robinson, Terry E.
通讯作者：
Robinson, Terry E.
DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
Barrot, M;Olivier, JDA;Nestler, EJ
通讯作者：
Nestler, EJ