Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine
OpenAlex – February 13, 2017
Source: OpenAlex
Summary
A striking 934 out of 6,728 identified proteins in human cerebral organoids showed differential expression after treatment with the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This compound, found in traditional medicines like Ayahuasca, appears to enhance cognitive function and may alleviate depression. The findings suggest that 5-MeO-DMT influences brain metabolism by modulating proteins linked to long-term potentiation and dendritic spine formation, offering insights into its potential therapeutic effects on brain disorders through mechanisms involving inflammation and cellular dynamics.
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.