Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT
Using shotgun mass spectrometry on human cerebral organoids treated with 5‑MeO‑DMT, the study identified 6,728 proteins of which 934 were differentially expressed, revealing anti‑inflammatory signatures and modulation of proteins linked to long‑term potentiation, dendritic spine formation and cytoskeletal/microtubule dynamics. This provides the first molecular insight into how 5‑MeO‑DMT alters human brain‑like tissue.
Authors
- Sidarta Ribeiro
- Draulio Araújo
Published
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.
Research Summary of 'Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT'
Introduction
Earlier research has identified dimethyltryptamines — including N,N-DMT, 5-HO-DMT and 5-MeO-DMT — as serotonin-like entheogens with reported antidepressant and cognitive effects and with activity at serotonin (5-HT) receptors and sigma-1 receptors (σ-1R). However, legal constraints and a lack of suitable human experimental models have limited mechanistic understanding of how these compounds alter human brain biology. Advances in differentiation of human pluripotent stem cells into three-dimensional cerebral organoids provide a system that recapitulates multiple brain cell types and aspects of cortical architecture, offering a platform to study drug effects on human neural tissue and plasticity that may not be captured in simple monolayer cultures or animal models. Dakic and colleagues set out to characterise short-term molecular effects of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human neural preparations, comparing simple human neural progenitor cell (hNPC) monolayers with 3D cerebral organoids. Using unbiased, mass spectrometry-based shotgun proteomics, the study aimed to identify proteome-wide changes after a 24-hour exposure and to infer affected pathways related to inflammation, synaptic plasticity (including long-term potentiation, LTP), cytoskeletal dynamics and cell survival.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Dakic, V., Minardi Nascimento, J., Costa Sartore, R., Maciel, R. D. M., de Araujo, D. B., Ribeiro, S., Martins-de-Souza, D., & Rehen, S. K. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-12779-5
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