Harmine stimulates proliferation of human neural progenitors
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 patien...
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PeerJ Inc.
2016-12-01
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| Online Access: | https://peerj.com/articles/2727.pdf |
| _version_ | 1797418764670599168 |
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| author | Vanja Dakic Renata de Moraes Maciel Hannah Drummond Juliana M. Nascimento Pablo Trindade Stevens K. Rehen |
| author_facet | Vanja Dakic Renata de Moraes Maciel Hannah Drummond Juliana M. Nascimento Pablo Trindade Stevens K. Rehen |
| author_sort | Vanja Dakic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T06:37:40Z |
| format | Article |
| id | doaj.art-da986dc44f3b456280b51617789cd9f1 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:37:40Z |
| publishDate | 2016-12-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-da986dc44f3b456280b51617789cd9f12023-12-03T10:55:47ZengPeerJ Inc.PeerJ2167-83592016-12-014e272710.7717/peerj.2727Harmine stimulates proliferation of human neural progenitorsVanja Dakic0Renata de Moraes Maciel1Hannah Drummond2Juliana M. Nascimento3Pablo Trindade4Stevens K. Rehen5IDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilIDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilIDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilIDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilIDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilIDOR, D’Or Institute for Research and Education, Rio de Janeiro, RJ, BrazilHarmine 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.https://peerj.com/articles/2727.pdfProliferationAntidepressantDYRK1AhNPCAyahuasca |
| spellingShingle | Vanja Dakic Renata de Moraes Maciel Hannah Drummond Juliana M. Nascimento Pablo Trindade Stevens K. Rehen Harmine stimulates proliferation of human neural progenitors PeerJ Proliferation Antidepressant DYRK1A hNPC Ayahuasca |
| title | Harmine stimulates proliferation of human neural progenitors |
| title_full | Harmine stimulates proliferation of human neural progenitors |
| title_fullStr | Harmine stimulates proliferation of human neural progenitors |
| title_full_unstemmed | Harmine stimulates proliferation of human neural progenitors |
| title_short | Harmine stimulates proliferation of human neural progenitors |
| title_sort | harmine stimulates proliferation of human neural progenitors |
| topic | Proliferation Antidepressant DYRK1A hNPC Ayahuasca |
| url | https://peerj.com/articles/2727.pdf |
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