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5-MeO-DMT 诱导的人类类器官蛋白质组的短期变化。

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

机构信息

D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.

Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Sci Rep. 2017 Oct 9;7(1):12863. doi: 10.1038/s41598-017-12779-5.

DOI:10.1038/s41598-017-12779-5
PMID:28993683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5634411/
Abstract

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.

摘要

色胺类物质是存在于传统美洲原住民医学中的具有致幻作用的血清素类似物，最近与认知增益、抗抑郁作用以及与注意力相关的大脑区域变化有关。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类大脑代谢的理解。在这里，我们使用鸟枪法质谱法来探索 5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）对人神经类器官诱导的蛋白质组学差异。在鉴定出的 6728 种蛋白质中，有 934 种在 5-MeO-DMT 处理的神经类器官中表达差异。计算机分析加强了 5-MeO-DMT 的抗炎作用，并揭示了对与长时程增强、树突棘形成相关的蛋白质的调节作用，包括参与细胞突起形成、微管动力学和细胞骨架重排的蛋白质。我们的数据首次提供了关于 5-MeO-DMT 在人神经类器官中引起的分子变化的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/8e33a766988f/41598_2017_12779_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/e8c52803f569/41598_2017_12779_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/731c4c66ae11/41598_2017_12779_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/8b66dab29cc6/41598_2017_12779_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/0cd95bd86380/41598_2017_12779_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/f74ac3b00948/41598_2017_12779_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/8e33a766988f/41598_2017_12779_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/e8c52803f569/41598_2017_12779_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/731c4c66ae11/41598_2017_12779_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/8b66dab29cc6/41598_2017_12779_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/0cd95bd86380/41598_2017_12779_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/f74ac3b00948/41598_2017_12779_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5634411/8e33a766988f/41598_2017_12779_Fig6_HTML.jpg

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