Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice.
Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice.
复制标题
伏核中潜在的 Ago2/miR-3068-5p 级联有助于甲基苯丙胺诱导的小鼠运动敏化。
DOI：
10.3389/fphar.2021.708034
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发表时间：
2021
影响因子：
5.6
通讯作者：
Chen T
中科院分区：
文献类型：
--
作者：
Liu D;Liang M;Zhu L;Zhou TT;Wang Y;Wang R;Wu FF;Goh ELK;Chen T
microRNA（miRNA）生物发生的失调与药物成瘾有关。 Argonaute2（AGO2）是一种参与miRNA产生的特定剪接蛋白，在我们先前的研究中发现甲基苯丙胺（METH）敏感的小鼠的伏隔核（NAC）失调。在这里，我们确定了NAC中的AGO2是否调节小鼠中的甲基化敏化并鉴定出参与此过程的AGO2依赖性miRNA。在反复使用METH后，我们发现NAC中AGO2表达的逐渐降低。通过击倒NAC神经元水平的AGO2，可以增强甲基诱导的小鼠诱导的超球活性，但通过在NAC神经元中过度表达AGO2来降低。令人惊讶的是，MiR-3068-5p在过表达AGO2后被上调，并在NAC中被沉默的AGO2下调。将miR-3068-5p击倒，作为AGO2依赖性miRNA，增强了小鼠的甲基敏化反应。这些发现表明，NAC中神经元中的AGO2失调能够调节METH敏化，并提出了AGO2依赖性miR-3068-5p在甲基化敏化中的潜在作用。
Dysregulation of microRNA (miRNA) biogenesis is involved in drug addiction. Argonaute2 (Ago2), a specific splicing protein involved in the generation of miRNA, was found to be dysregulated in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice in our previous study. Here, we determined whether Ago2 in the NAc regulates METH sensitization in mice and identified Ago2-dependent miRNAs involved in this process. We found a gradual reduction in Ago2 expression in the NAc following repeated METH use. METH-induced hyperlocomotor activity in mice was strengthened by knocking down NAc neuronal levels of Ago2 but reduced by overexpressing Ago2 in NAc neurons. Surprisingly, miR-3068-5p was upregulated following overexpression of Ago2 and downregulated by silencing Ago2 in the NAc. Knocking down miR-3068-5p, serving as an Ago2-dependent miRNA, strengthened the METH sensitization responses in mice. These findings demonstrated that dysregulated Ago2 in neurons in the NAc is capable of regulating METH sensitization and suggested a potential role of Ago2-dependent miR-3068-5p in METH sensitization.
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DOI：
10.1016/j.bbi.2009.12.008
发表时间：
2010-03
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Buchanan JB;Sparkman NL;Johnson RW
通讯作者：
Johnson RW
树突状GABA能抑制的输入特异性NMDAR依赖性增强。
影响因子：
16.2
作者：
Chiu CQ;Martenson JS;Yamazaki M;Natsume R;Sakimura K;Tomita S;Tavalin SJ;Higley MJ
通讯作者：
Higley MJ
影响因子：
7.3
作者：
Garcia-Perez, D.;Saez-Belmonte, F.;Milanes, M. V.
通讯作者：
Milanes, M. V.
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
56.9
作者：
Knight, SW;Bass, BL
通讯作者：
Bass, BL