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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 via OpenAlex

Summary

AI-generated from the abstract

5-MeO-DMT, a hallucinogenic molecule found in traditional Amerindian medicine, alters the proteome of human cerebral organoids. Of 6,728 identified proteins, 934 were differentially expressed after treatment. Systems biology analyses indicate anti-inflammatory effects and modulation of proteins linked to long-term potentiation, dendritic spine formation, cellular protrusion, microtubule dynamics, and cytoskeletal reorganization. These findings provide mechanistic insights into the neuropsychological changes associated with dimethyltryptamine ingestion.

Study at a glance

Characteristics Experimental study
Population Human cerebral organoids
Interventions 5-methoxy-N N-dimethyltryptamine (5-MeO-DMT)
Keywords Proteome Organoid Human brain Hallucinogen Dendritic spine
Key finding 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.

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