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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

Vanja Dakic, View ORCID ProfileJuliana Minardi Nascimento, Rafaela Costa Sartore, Renata de Moraes Maciel, Draulio B. de Araujo, Sidarta Ribeiro, View ORCID ProfileDaniel Martins-de-Souza, View ORCID ProfileStevens Rehen
doi: https://doi.org/10.1101/108159
Vanja Dakic
1D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil;
2Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
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Juliana Minardi Nascimento
1D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil;
3Laboratory of Neuroproteomics, Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil;
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  • ORCID record for Juliana Minardi Nascimento
Rafaela Costa Sartore
1D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil;
2Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
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Renata de Moraes Maciel
1D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil;
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Draulio B. de Araujo
4Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil
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Sidarta Ribeiro
4Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil
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Daniel Martins-de-Souza
3Laboratory of Neuroproteomics, Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil;
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Stevens Rehen
1D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil;
2Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
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  • For correspondence: srehen@lance-ufrj.org
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Abstract

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.

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Posted February 13, 2017.
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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine
Vanja Dakic, Juliana Minardi Nascimento, Rafaela Costa Sartore, Renata de Moraes Maciel, Draulio B. de Araujo, Sidarta Ribeiro, Daniel Martins-de-Souza, Stevens Rehen
bioRxiv 108159; doi: https://doi.org/10.1101/108159
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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine
Vanja Dakic, Juliana Minardi Nascimento, Rafaela Costa Sartore, Renata de Moraes Maciel, Draulio B. de Araujo, Sidarta Ribeiro, Daniel Martins-de-Souza, Stevens Rehen
bioRxiv 108159; doi: https://doi.org/10.1101/108159

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