Harmine stimulates neurogenesis of human neural cells in vitro

Harmine, a β-carboline alkaloid found in the psychotropic plant decoction Ayahuasca, increased the pool of proliferating human neural progenitor cells (hNPCs) by 57% after 4 days of treatment. The effect appears to be mediated through inhibition of the DYRK1A enzyme, as an analog that inhibits DYRK1A (INDY) similarly induced proliferation, while an inhibitor of monoamine oxidase (pargyline) did not. Harmine also increased dendritic arborization, including total neurite length, number of segments, extremities, and nodes in MAP2-positive neurons. These findings suggest a biological activity that may contribute to the antidepressant effects observed with Ayahuasca.

Study at a glance

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 .