Morphine modulates mouse hippocampal progenitor cell lineages by upregulating miR-181a level.
Morphine modulates mouse hippocampal progenitor cell lineages by upregulating miR-181a level.
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DOI：
10.1002/stem.1774
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发表时间：
2014-11
期刊：
影响因子：
5.2
通讯作者：
Law, Ping-Yee
中科院分区：
文献类型：
--
作者：
Xu, Chi;Zhang, Yue;Zheng, Hui;Loh, Horace H.;Law, Ping-Yee
吗啡等成瘾药物调节成人神经发生的机制仍然难以捉摸。我们现在证明吗啡可以通过控制 miR-181a 和随后的海马神经祖细胞 (hNPC) 谱系来调节神经发生。在吗啡存在的情况下，hNPC 优先分化为星形胶质细胞，这种效应被特定的 μ-阿片受体拮抗剂 Cys2-Tyr3-Orn5-Pen7-amide 阻断。这种效应是由 Prox1/Notch1 通路介导的，如吗啡处理但芬太尼处理的 hNPC 中 Notch1 水平增加所证明，并被 Notch1 siRNA 的过度表达所阻断。 Prox1 siRNA 的过度表达上调了 Notch1 水平并增强了吗啡诱导的谱系变化。 Prox1 转录水平由 miR-181a 与其 3'UTR 序列之间的直接相互作用调节。用吗啡进行体外和体内治疗分别导致 hNPC 和小鼠海马中 miR-181a 水平增加。 miR-181a 的过度表达模拟降低了 Prox1 水平、增加了 Notch1 水平并增强了 hNPC 向星形胶质细胞的分化。同时，miR-181a抑制剂的过度表达提高了Prox1水平，降低了Notch1水平，并随后阻断了吗啡诱导的谱系变化。因此，通过 miR-181a 调节 Prox1/Notch1 活性，吗啡影响 hNPC 分化的命运，从而影响成熟神经元和星形胶质细胞的最终数量。
The mechanism by which addictive drugs such as morphine regulate adult neurogenesis remains elusive. We now demonstrate that morphine can regulate neurogenesis by control of miR-181a and subsequent hippocampal neural progenitor cell (hNPC) lineages. In the presence of morphine, hNPCs preferentially differentiated into astrocytes, an effect blocked by the specific μ-opioid receptor antagonist, Cys2-Tyr3-Orn5-Pen7-amide. This effect was mediated by the Prox1/Notch1 pathway as demonstrated by an increase in Notch1 level in the morphine- but not fentanyl-treated hNPCs, and blocked by over-expression of Notch1 siRNA. Over-expression of Prox1 siRNA up-regulated Notch1 level and potentiated the morphine-induced lineage changes. Prox1 transcript level was regulated by direct interaction between miR-181a and its 3′UTR sequence. In vitro and in vivo treatment with morphine resulted in an increase in miR-181a level in hNPCs and mouse hippocampi, respectively. Over-expression of miR-181a mimics reduced Prox1 levels, increased Notch1 levels and enhanced hNPCs differentiation into astrocytes. Meanwhile, over-expression of the miR-181a inhibitor raised Prox1 levels, decreased Notch1 levels and subsequently blocked the morphine-induced lineage changes. Thus, by modulating Prox1/Notch1 activities via miR-181a, morphine influences the fate of differentiating hNPCs differentiation and therefore the ultimate quantities of mature neurons and astrocytes.
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DOI：
10.1073/pnas.120552597
发表时间：
2000-06-20
影响因子：
11.1
作者：
Eisch, AJ;Barrot, M;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
1.7
作者：
Jang, MH;Shin, MC;Kim, CJ
通讯作者：
Kim, CJ
影响因子：
4.2
作者：
Ge, WH;Martinowich, K;Sun, YE
通讯作者：
Sun, YE
影响因子：
6.2
作者：
Hwang, Cheol Kyu;Wagley, Yadav;Law, Ping-Yee;Wei, Li-Na;Loh, Horace H.
通讯作者：
Loh, Horace H.
影响因子：
14.8
作者：
Chojnacki, Andrew;Weiss, Samuel
通讯作者：
Weiss, Samuel