RT Journal Article
SR Electronic
T1 Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 108159
DO 10.1101/108159
A1 Vanja Dakic
A1 Juliana Minardi Nascimento
A1 Rafaela Costa Sartore
A1 Renata de Moraes Maciel
A1 Draulio B. de Araujo
A1 Sidarta Ribeiro
A1 Daniel Martins-de-Souza
A1 Stevens Rehen
YR 2017
UL http://biorxiv.org/content/early/2017/02/13/108159.abstract
AB Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca, Virola) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention, self-referential thought, and internal mentation. 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 dimethyltryptamine (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 the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. Proteins involved in long-term potentiation were modulated in a complex manner, with significant increases in the levels of NMDAR, CaMKII and CREB, but a reduction of PKA and PKC levels. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.