Harmine stimulates proliferation of human neural progenitors

Harmine is the -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 patient...

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Bibliographic Details
Published in:PeerJ (San Francisco, CA) CA), 2016-12, Vol.4, p.e2727-e2727, Article e2727
Main Authors: Dakic, Vanja, Maciel, Renata de Moraes, Drummond, Hannah, Nascimento, Juliana M, Trindade, Pablo, Rehen, Stevens K
Format: Article
Language:English
Subjects:
Amine oxidase (flavin-containing)
Antidepressant
Antidepressants
Apoptosis
Ayahuasca
Biology
Cell Biology
Cell cycle
Cell growth
Cell proliferation
Depression (Mood disorder)
Developmental Biology
DYRK1A
hNPC
Kinases
Medical research
Mental depression
Monoamine oxidase
Nestin
Neural stem cells
Neurobiology
Neurogenesis
Neurons
Neuroscience
Neurosciences
Pargyline
Phosphorylation
Pluripotency
Proliferation
Rodents
Stem cells
Tyrosine
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Summary:Harmine is the -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 and antidepressant effects .
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.2727