Navegando por Autor "Martins-de-Souza, Daniel"
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Artigo Nootropic effects of LSD: Behavioral, molecular and computational evidence(Elsevier BV, 2022-06-19) Ornelas, Isis M; Silva, Felipe Augusto Cini da; Wießner, Isabel; Marcos, Encarni; Araujo, Draulio Barros de; Goto-Silva, Livia; Nascimento, Juliana; Silva, Sérgio Ruschi Bergamachi; Costa, Marcelo N; Falchi, Marcelo; Olivieri, Rodolfo; Fontes, Fernanda Palhano Xavier de; Sequerra, Eduardo Bouth; Martins-de-Souza, Daniel; Feilding, Amanda; Costa, César Rennó; Tófoli, Luis Fernando; Rehen, Stevens K; Ribeiro, Sidarta Tollendal GomesThe therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we show that LSD treatment enhanced performance in a novel object recognition task in rats, and in a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. To gain insight into the relation of neural plasticity, aging and LSD-induced cognitive gains, we emulated the experiments in rats and humans with a neural network model of a cortico-hippocampal circuit. Using the baseline strength of plasticity as a proxy for age and assuming an increase in plasticity strength related to LSD dose, the simulations provided a good fit for the experimental data. Altogether, the results suggest that LSD has nootropic effectsArtigo Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT(2017-10-09) Dakic, Vanja; Nascimento, Juliana Minardi; Sartore, Rafaela Costa; Maciel, Renata de Moraes; Araújo, Dráulio Barros de; Ribeiro, Sidarta Tollendal Gomes; Martins-de-Souza, Daniel; Rehen, Stevens K.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.