Stevens Rehen

Stevens Rehen is a stem cell biologist and professor at the Institute of Biomedical Sciences, Federal University of Rio de Janeiro. He is Head of Research at D’Or Institute for Research and Education (IDOR), Brazil, Affiliated Member of the Latin American Academy of Sciences and the Academy of Sciences for the Developing World and former President of the Brazilian Society for Neuroscience and Behavior.

My goal is to push the boundaries of neuroscience by applying new cellular models. We have been successfully studying several aspects of neurogenesis using organoids. Notably, considerable research efforts have been dedicated to the impacts of Zika virus infection and psychedelics for the human brain tissue. Twenty years ago, as a postdoctoral fellow in US, I carried out research using cerebral cortex explants and neuronal cells to describe chromosomal aneuploidies in the brain, a type of somatic mosaicism. Back in Rio de Janeiro, we were pioneers in stem cell research, contributing with a significant part of scientific publications in the field, establishing the regulatory aspects of stem cell research and advising many students and postdocs in Brazil.

Biological Effects of Psychedelics in Human Neural Stem Cells and Brain Organoids.

For more than four decades, restrictions on research with psychedelics have abrogated the comprehension of how such substances impact brain metabolism. Besides the historical restrictions, studies have also been compromised by limitations of adequate models. In the last few years, progress has been made regarding the differentiation of human induced pluripotent stem (iPS) cells into neural stem cells and brain organoids. These approaches recreate features of the cerebral cortex development, showing potential for human brain modeling studies. Here, I will present our recent data regarding the effects of the β-carboline alkaloid harmine, N,N-dimethyltryptamine (NN-DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in human neural tissues. Harmine increased the pool of neural progenitor cells by inhibiting DYRK1A (dual specificity tyrosine-phosphorylation-regulated kinase). NN-DMT increased the number of neural stem cells, in a dose dependent manner, through the activation of 5HT2A receptor. These results suggest that harmine and NN-DMT may influence neurogenesis , which is probably associated with the antidepressant effects of Ayahuasca described in patients. Moreover, human neurons exposed to NN-DMT showed increased expression of synaptophysin, while analyses of brain organoids exposed to 5-MeO-DMT revealed proteins broadly distributed on functional activities such as cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. These data contribute to elucidate neuroplasticity signaling pathways influenced by dimethyltryptamines. Human iPS brain cells offer an exciting new range of opportunities to investigate the influence of psychedelics in the central nervous system.