Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT.

Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT.
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DOI:
10.1038/s41598-017-12779-5
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发表时间:
2017-10-09
期刊:
影响因子:
4.6
通讯作者:
Rehen SK
Rehen SK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dakic V;Minardi Nascimento J;Costa Sartore R;Maciel RM;de Araujo DB;Ribeiro S;Martins-de-Souza D;Rehen SK

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二甲基色胺是一种存在于传统美洲药物中的催产性5-羟色胺样分子,最近与认知获得、抗抑郁作用和与注意力相关的大脑区域的变化有关。法律限制和缺乏足够的实验模型限制了人们对这些物质如何影响人脑新陈代谢的理解。在这里,我们使用鸟枪质谱仪来研究5-甲氧基-N,N-二甲基色胺(5-MeO-DMT)对人脑器官的蛋白质组差异。在6728个已鉴定的蛋白质中,有934个在5-MeO-DMT处理的脑器官中有差异表达。在计算机分析中,强化了先前报道的5-MeO-DMT的抗炎作用,并揭示了对与长时程增强、树突棘的形成相关的蛋白质的调制作用,包括那些参与细胞突起形成、微管动力学和细胞骨架重组的蛋白质。我们的数据首次提供了关于5-MeO-DMT在人脑器官中引起的分子变化的见解。
Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico analysis reinforced previously reported anti-inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids.
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