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Harmine stimulates neurogenesis of human neural cells in vitro

Vanja Dakic, Renata de Moraes Maciel, Hannah Drummond, Juliana Nascimento, Pablo Trindade, Stevens K. Rehen

April 14, 2016 DOI: 10.7287/peerj.preprints.1957 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vitro study
Population Human neural progenitor cells (hNPCs) derived from pluripotent stem cells
Intervention Harmine
Duration 4 days of treatment
Topics Neuroplasticity
Keywords Harmine Neural stem cell Pharmacology Pargyline Cell growth Creb Harmaline Convulsant In vivo Monoamine oxidase inhibitor Cell biology
Citations 1
Key points Harmine enhances proliferation of human neural progenitor cells by 57% and increases dendritic arborization, likely through inhibition of DYRK1A.

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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