Harmine stimulates proliferation of human neural progenitors

PeerJ. 2016 Dec 6:4:e2727. doi: 10.7717/peerj.2727. eCollection 2016.


Harmine is the β-carboline alkaloid with the 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 71.5%. 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. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Keywords: Antidepressant; Ayahuasca; DYRK1A; Proliferation; hNPC.

Grants and 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 (grant 2014/21035-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.