Harmine stimulates proliferation of human neural progenitors

Abstract

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.

The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro

“…Our results for the effect of harmine on proliferation are in line with a previous study showing harmine-induced increase in mitosis in cultured chick embryo cells 32 , and in human neural progenitor cells 33 . To our knowledge, the effects of harmaline and THH on neurogenesis have not been studied before.…”

Ayahuasca: what mental health professionals need to know

“…Recent reports suggest the possible role of harmine in neurogenesis 69 . Furthermore, it is known that DMT act as an agonist at 5-HT 1A receptors 8,70 .…”

“…The fact is that we still do not know what DMT is doing in our bodies, so this is a very interesting topic to further investigate 9,10 . Moreover, preclinical studies suggest that DMT and the β-carbolines have not only antidepressive, anxiolytic, and antiaddictive proprieties 39,40 , but also neuroprotective and neurotrophic potentials 69,[77][78][79] . For instance, a recent neuropsychological study in ayahuasca user suggested that ayahuasca may indeed improve cognition and have "nootropic" effect 80 .…”

Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

“…To induce hESCs towards neural differentiation, we adapted Baharvand and coworkers' protocol (Baharvand et al 2007;Dakic et al 2016). Briefly, 70%…”

“…hNPCs were expanded for no more than 5 passages. Basic characterization of this culture was published in Dakic et al, 2016.…”