Harmine stimulates neurogenesis of human neural cells in vitro
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Abstract
Harmine is a β-carboline alkaloid present at highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 57%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY) and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of Dyrk1a is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Harmine also increased dendritic arborization, including total neurite length, number of segments, extremities and nodes in MAP2 positive neurons. Our findings show that harmine enhances neurogenesis of hNPCs in vitro, and suggest a biological activity associated with its antidepressant effects in vivo.
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2016. Harmine stimulates neurogenesis of human neural cells in vitro. PeerJ Preprints 4:e1957v1 https://doi.org/10.7287/peerj.preprints.1957v1Author comment
This is a preprint submission to PeerJ preprints
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Vanja Dakic conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Renata de Moraes Maciel conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, reviewed drafts of the paper.
Hannah Drummond performed the experiments, reviewed drafts of the paper.
Juliana M Nascimento prepared figures and/or tables, reviewed drafts of the paper.
Pablo Trindade wrote the paper, reviewed drafts of the paper.
Stevens K Rehen conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.
Funding
This study was funded by the following Brazilian funding agencies: National Council for Scientific and Technological Development (CNPq), Foundation for Research Support in the State of Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Funding Authority for Studies and Projects (FINEP), Brazilian Development Bank (BNDES) and São Paulo Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
