Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons.
Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons.
复制标题
DOI：
10.1038/s41380-021-01328-2
复制
发表时间：
2022-03
影响因子：
11
通讯作者：
Caboche, Jocelyne
中科院分区：
文献类型：
--
作者：
Forget, Benoit;Garcia, Elena Martin;Godino, Arthur;Rodriguez, Laura Domingo;Kappes, Vincent;Poirier, Pierre;Andrianarivelo, Andry;Marchan, Eric Senabre;Allichon, Marie-Charlotte;Marias, Melanie;Vanhoutte, Peter;Girault, Jean-Antoine;Maldonado, Rafael;Caboche, Jocelyne
药物成瘾的持久性和经验依赖性可能部分来自表观遗传学改变，包括非编码微RNA（miRNA），这对神经元功能至关重要，并受纹状体中可卡因的调节。两个主要的纹状体细胞群，纹状体黑质和纹状体苍白球投射神经元，分别表达，D1（D1-SPNs）和D2（D2-SPNs）多巴胺受体，并显示不同的，但在药物诱发的反应互补的功能。然而，miRNAs作用的细胞类型特异性作用尚未阐明。在这里，我们评估了一个子集的miRNA的表达，提出了调节可卡因的影响，在持续的可卡因暴露在小鼠的延髓核（NAc）和背侧纹状体（DS），并表明这些选定的miRNA优先上调NAc。我们重点关注miR-1，考虑到其一些预测的mRNA靶点Fosb和Npas 4在可卡因作用中的重要作用。我们在体外和体内验证了这些靶点。我们通过在特定的纹状体细胞群中过表达miR-1来探索其调节可卡因诱导的行为的潜力。在DS D1-SPN中，miR-1过表达下调Fosb和Npas 4，减少可卡因诱导的CPP恢复，但增加线索诱导的可卡因寻求。在DS D2-SPN中，miR-1过表达降低了自我施用可卡因的动机。我们的研究结果表明miR-1及其靶基因Fosb和Npas 4在这些行为中的作用，并强调了miR-1的精确细胞类型和区域特异性调节作用，说明了细胞特异性研究的重要性。
The persistent and experience-dependent nature of drug addiction may result in part from epigenetic alterations, including non-coding micro-RNAs (miRNAs), which are both critical for neuronal function and modulated by cocaine in the striatum. Two major striatal cell populations, the striato-nigral and striato-pallidal projection neurons, express, respectively, the D1 (D1-SPNs) and D2 (D2-SPNs) dopamine receptor, and display distinct but complementary functions in drug-evoked responses. However, a cell-type-specific role for miRNAs action has yet to be clarified. Here, we evaluated the expression of a subset of miRNAs proposed to modulate cocaine effects in the nucleus accumbens (NAc) and dorsal striatum (DS) upon sustained cocaine exposure in mice and showed that these selected miRNAs were preferentially upregulated in the NAc. We focused on miR-1 considering the important role of some of its predicted mRNA targets, Fosb and Npas4, in the effects of cocaine. We validated these targets in vitro and in vivo. We explored the potential of miR-1 to regulate cocaine-induced behavior by overexpressing it in specific striatal cell populations. In DS D1-SPNs miR-1 overexpression downregulated Fosb and Npas4 and reduced cocaine-induced CPP reinstatement, but increased cue-induced cocaine seeking. In DS D2-SPNs miR-1 overexpression reduced the motivation to self-administer cocaine. Our results indicate a role of miR1 and its target genes, Fosb and Npas4, in these behaviors and highlight a precise cell-type- and region-specific modulatory role of miR-1, illustrating the importance of cell-specific investigations.
登录
查看更多内容
DOI：
10.1016/j.pnpbp.2018.01.002
发表时间：
2018-12-20
影响因子：
5.6
作者：
Farrell MR;Schoch H;Mahler SV
通讯作者：
Mahler SV
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：
25
作者：
Bock, Roland;Shin, J. Hoon;Kaplan, Alanna R.;Dobi, Alice;Markey, Eric;Kramer, Paul F.;Gremel, Christina M.;Christensen, Christine H.;Adrover, Martin F.;Alvarez, Veronica A.
通讯作者：
Alvarez, Veronica A.
影响因子：
64.8
作者：
Cui, Guohong;Jun, Sang Beom;Jin, Xin;Pham, Michael D.;Vogel, Steven S.;Lovinger, David M.;Costa, Rui M.
通讯作者：
Costa, Rui M.
影响因子：
16.2
作者：
Bromberg-Martin, Ethan S.;Matsumoto, Masayuki;Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide