title: Harmine stimulates proliferation of human neural progenitors.
abstract: Harmine is theβ-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 proliferationin vitroand antidepressant effectsin vivo.
authors.affiliation: IDOR, D'Or Institute for Research and Education, Rio de Janeiro, RJ, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Vanja
authors.initials: V
authors.lastname: Dakic
authors.affiliation: IDOR, D'Or Institute for Research and Education , Rio de Janeiro , RJ , Brazil.
authors.forename: Renata de Moraes
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: IDOR, D'Or Institute for Research and Education, Rio de Janeiro, RJ, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Hannah
authors.initials: H
authors.lastname: Drummond
authors.affiliation: IDOR, D'Or Institute for Research and Education, Rio de Janeiro, RJ, Brazil; Department of Biochemistry and Tissue Biology/Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Nascimento
authors.affiliation: IDOR, D'Or Institute for Research and Education , Rio de Janeiro , RJ , Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Trindade
authors.affiliation: IDOR, D'Or Institute for Research and Education, Rio de Janeiro, RJ, Brazil; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Stevens K
authors.initials: SK
authors.lastname: Rehen
keywords: Antidepressant; Ayahuasca; DYRK1A; Proliferation; hNPC