Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes.
Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes.
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青藤碱通过 NMDAR1/CAMKII/CREB 途径防止吗啡依赖：星形胶质细胞来源的外泌体的可能作用
DOI：
10.3390/molecules23092370
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发表时间：
2018-09-17
期刊：
影响因子：
--
通讯作者：
Mo Z
中科院分区：
文献类型：
--
作者：
Ou J;Zhou Y;Li C;Chen Z;Li H;Fang M;Zhu C;Huo C;Yung KK;Li J;Luo C;Mo Z
青藤碱是一种非成瘾性生物碱，用于预防吗啡依赖，尽管其机制尚未完全了解。在中枢神经系统疾病中，星形胶质细胞通过外泌体加重周围细胞的病理过程。然而，青藤碱对星形胶质细胞源性外泌体改善吗啡依赖的作用尚未见报道。在这项研究中，我们发现青藤碱可以预防吗啡诱导的小鼠条件性位置偏爱。青藤碱可降低吗啡处理的SH-SY 5 Y细胞内cAMP和Ca ~（2+）水平。青藤碱可抑制吗啡依赖小鼠海马和SH-SY 5 Y细胞中p-NMDAR 1/NMDAR 1、p-CAMK Ⅱ/CAMK Ⅱ和p-CREB/CREB的表达。此外，我们还发现青藤碱在体内和体外均能抑制吗啡诱导的星形胶质细胞活化。然后，从用磷酸盐缓冲盐水（PBS，ctl-exo）、吗啡（mor-exo）或吗啡和青藤碱（Sino-exo）处理的培养的原代星形胶质细胞中分离外泌体。随后，用ctl-exo、mor-exo和Sino-exo处理吗啡处理的SH-SY 5 Y细胞。结果表明，Sino-exo可降低吗啡处理的SH-SY 5 Y细胞内cAMP、Ca ~（2+）水平及p-CAMK Ⅱ/CAMK Ⅱ和p-CREB/CREB的表达。总之，我们证明青藤碱通过NMDAR 1/CAMK II/CREB通路在体内和体外对吗啡依赖具有保护作用。青藤碱对星形胶质细胞来源exosomes功能的影响可能与其抗吗啡依赖作用有关。
Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence.
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影响因子：
34.7
作者：
Lisman, John;Yasuda, Ryohei;Raghavachari, Sridhar
通讯作者：
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DOI：
10.1016/j.pnpbp.2018.02.009
发表时间：
2018-08-30
影响因子：
5.6
作者：
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通讯作者：
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DOI：
10.1101/lm.042192.116
发表时间：
2016-10
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
2.7
作者：
Haghparast, Abbas;Taslimi, Zahra;Hassanpour-Ezatti, Majid
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