Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT

Author(s)

Dakic, Vanja ^{[1, 2]} ; Nascimento, Juliana Minardi ^{[2, 3]} ; Sartore, Rafaela Costa ^{[1, 2]} ; Maciel, Renata de Moraes ^[2] ; de Araujo, Draulio B. ^[4] ; Ribeiro, Sidarta ^[4] ; Martins-de-Souza, Daniel ^{[3, 5]} ; Rehen, Stevens K. ^{[1, 2]}

Affiliation

^[1] Univ Fed Rio de Janeiro, Inst Biomed Sci, Rio De Janeiro - Brazil

^[2] DOr Inst Res & Educ IDOR, Rio De Janeiro - Brazil

^[3] Univ Campinas UNICAMP, Dept Biochem & Tissue Biol, Inst Biol, Lab Neuroprote, Campinas, SP - Brazil

^[4] Univ Fed Rio Grande do Norte, Brain Inst, Natal, RN - Brazil

^[5] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria INBION, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, OCT 9 2017.
• Web of Science Citations: 12

Abstract

Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional Amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. Legal restrictions and the lack of adequate experimental models have limited the understanding of 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 analysis reinforced previously reported anti-inflammatory actions of 5-MeO-DMT and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. Our data offer the first insight about molecular alterations caused by 5-MeO-DMT in human cerebral organoids. (AU)

• FAPESP's process: 14/21035-0 - Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients
• Grantee: Juliana Minardi Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants