Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine
Vanja Dakic, Juliana Nascimento, Rafaela Sartore, Renata de Moraes Maciel, Dráulio Barros de Araújo, Sidarta Ribeiro, Daniel Martins-de-Souza, Stevens K. Rehen
bioRxiv (Cold Spring Harbor Laboratory) February 13, 2017 preprint DOI: 10.1101/108159 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Human cerebral organoids |
| Interventions | 5-methoxy-N N-dimethyltryptamine (5-MeO-DMT) |
| Topics | 5-MeO-DMT DMT |
| Keywords | Proteome Organoid Human brain Hallucinogen Dendritic spine Proteomics Long-term potentiation Cell biology Molecular neuroscience Computational biology |
| Key findings | 5-MeO-DMT differentially expressed 934 proteins in human cerebral organoids, modulating proteins associated with long-term potentiation, dendritic spine formation, and cytoskeletal reorganization. |
Abstract
Abstract Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention. Historical and technical restrictions impaired understanding 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 systems biology analyses support 5-MeO-DMT’s anti-inflammatory effects and reveal a modulation of proteins associated with long-term potentiation, the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.