Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation.
Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation.
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甲基苯丙胺相关的记忆受作者和允许组蛋白甲基化的橡皮擦调节。
DOI：
10.1016/j.biopsych.2013.09.014
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发表时间：
2014-07-01
影响因子：
10.6
通讯作者：
Miller, Courtney A.
中科院分区：
文献类型：
--
作者：
Aguilar-Valles, Argel;Vaissiere, Thomas;Griggs, Erica M.;Mikaelsson, Mikael A.;Takacs, Irma F.;Young, Erica J.;Rumbaugh, Gavin;Miller, Courtney A.
与滥用药物相关的记忆，如甲基苯丙胺(冰毒)，通过引发渴望增加了对药物使用障碍的复发易感性。伏隔核(NAC)对这些药物相关的记忆是必不可少的，但其潜在的机制尚不清楚。翻译后染色质修饰，如组蛋白甲基化，调节基因转录，因此我们研究了相关的表观遗传修饰在冰毒相关记忆中的作用。使用条件性位置偏爱来评估NAC中支持冰毒相关记忆的表观遗传景观(n=79)。组蛋白甲基化(H3K4me2/3)对冰毒相关记忆的形成和表达的影响是由编写者在NAC内的局部敲除(KD)、甲基转移酶MLL1(n=26)和H3K4me2/3的组蛋白去甲基化酶KDM5C(n=38)确定的。对形成冰毒相关记忆的动物的NAC中染色质修改的调查显示，几种与活跃转录相关的修改都是全局诱导的。这与微阵列分析揭示的基因激活模式有关，包括OXTR和Fos的上调，其启动子也增加了H3K4me3。M111的KD降低了H3K4me3、Fos和OXTR的水平，并扰乱了冰毒相关的记忆。Kdm5c的Kd导致H3K4的高甲基化，并阻止冰毒相关记忆的表达。在NAC中，MLL1和KDM5C分别调节H3K4me2/3水平，支持甲基相关记忆的发育和表达。这些数据表明，允许的组蛋白甲基化，以及相关的表观遗传学编写器和擦除器，是治疗药物滥用复发的潜在靶点，药物滥用复发是一种由不想要的联想记忆持续存在的精神疾病。
Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder by triggering craving. The nucleus accumbens (NAc) is essential to these drug-associated memories, but underlying mechanisms are poorly understood. Posttranslational chromatin modifications, such as histone methylation, modulate gene transcription, thus we investigated the role of the associated epigenetic modifiers in METH-associated memory. Conditioned place preference was used to assess the epigenetic landscape in the NAc supporting METH-associated memory (n=79). The impact of histone methylation (H3K4me2/3) on the formation and expression of METH-associated memory was determined by focal, intra NAc knockdown (KD) of a writer, the methyltransferase MLL1 (n=26), and an eraser, the histone demethylase KDM5C (n=38), of H3K4me2/3. A survey of chromatin modifications in the NAc of animals forming a METH-associated memory revealed the global induction of several modifications associated with active transcription. This correlated with a pattern of gene activation, as revealed by microarray analysis, including upregulation of Oxtr and Fos, whose promoters also had increased H3K4me3. KD of Mll1 reduced H3K4me3, Fos and Oxtr levels and disrupted METH-associated memory. KD of Kdm5c resulted in hypermethylation of H3K4 and prevented the expression of METH-associated memory. The development and expression of METH-associated memory are supported by regulation of H3K4me2/3 levels by MLL1 and KDM5C, respectively, in the NAc. These data indicate that permissive histone methylation, and the associated epigenetic writers and erasers, represent potential targets for the treatment of substance abuse relapse, a psychiatric condition perpetuated by unwanted associative memories.
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影响因子：
2
作者：
Adegbola, Abidemi;Gao, Hanlin;Browning, Marsha
通讯作者：
Browning, Marsha
DOI：
10.1523/jneurosci.2107-11.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Corcoran KA;Donnan MD;Tronson NC;Guzmán YF;Gao C;Jovasevic V;Guedea AL;Radulovic J
通讯作者：
Radulovic J
影响因子：
5.3
作者：
Huang, Hsien-Sung;Matevossian, Anouch;Akbarian, Schahram
通讯作者：
Akbarian, Schahram
DOI：
10.1523/jneurosci.2873-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Griggs EM;Young EJ;Rumbaugh G;Miller CA
通讯作者：
Miller CA
影响因子：
64.5
作者：
Christensen, Jesper;Agger, Karl;Helin, Kristian
通讯作者：
Helin, Kristian