MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212.
MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212.
复制标题
DOI：
10.1038/nn.2615
复制
发表时间：
2010-09
影响因子：
25
通讯作者：
Kenny, Paul J.
中科院分区：
文献类型：
--
作者：
Im, Heh-In;Hollander, Jonathan A.;Bali, Purva;Kenny, Paul J.
X连锁转录抑制因子甲基CpG结合蛋白2（MeCP 2），已知其在神经发育障碍Rett综合征中的作用，正在成为有丝分裂后神经元神经可塑性的重要调节因子。可卡因成瘾通常被认为是一种神经可塑性障碍，但尚未探索MeCP 2的潜在参与。在这里，我们确定了MeCP 2在背侧纹状体中的关键作用，在长期接触药物的大鼠中观察到可卡因摄入量不断增加，这一过程模拟了人类成瘾者中越来越不受控制的可卡因使用。MeCP 2通过与microRNA-212（miR-212）的稳态相互作用来调节可卡因摄入，以控制可卡因对纹状体脑源性神经营养因子（BDNF）水平的影响。这些数据表明，MeCP 2和miR-212在背侧纹状体的稳态相互作用可能在调节可卡因成瘾的脆弱性中发挥重要作用。
The X-linked transcriptional repressor methyl CpG binding protein 2 (MeCP2), known for its role in the neurodevelopmental disorder Rett syndrome, is emerging as an important regulator of neuroplasticity in post-mitotic neurons. Cocaine addiction is commonly viewed as a disorder of neuroplasticity, but the potential involvement of MeCP2 has not been explored. Here we identify a key role for MeCP2 in the dorsal striatum in the escalating cocaine intake seen in rats with extended access to the drug, a process that mimics the increasingly uncontrolled cocaine use seen in human addicts. MeCP2 regulates cocaine intake through homeostatic interactions with microRNA-212 (miR-212) to control the effects of cocaine on striatal brain-derived neurotrophic factor (BDNF) levels. These data suggest that homeostatic interactions between MeCP2 and miR-212 in dorsal striatum may play an important role in regulating vulnerability to cocaine addiction.
登录
查看更多内容
DOI：
10.1523/jneurosci.2243-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jeanblanc J;He DY;Carnicella S;Kharazia V;Janak PH;Ron D
通讯作者：
Ron D
影响因子：
10.6
作者：
Graham, Danielle L.;Krishnan, Vaishnav;Larson, Erin B.;Graham, Ami;Edwards, Scott;Bachtell, Ryan K.;Simmons, Diana;Gent, Lana M.;Berton, Olivier;Bolanos, Carlos A.;DiLeone, Ralph J.;Parada, Luis F.;Nestler, Eric J.;Self, David W.
通讯作者：
Self, David W.
影响因子：
16.2
作者：
Chang, QA;Khare, G;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
3.3
作者：
Choi, KH;Whisler, K;Self, DW
通讯作者：
Self, DW
影响因子：
3.7
作者：
Abuhatzira, Liron;Makedonski, Kirill;Shemer, Ruth
通讯作者：
Shemer, Ruth