Title: Harmine stimulates neurogenesis of human neural cells in vitro
Vanja Dakic, Renata de Moraes Maciel, Hannah Drummond, Juliana Nascimento, Pablo Trindade, Stevens K. Rehen, Tissue Biology
April 14, 2016 DOI: 10.7287/peerj.preprints.1957v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell culture study |
|---|---|
| Population | Human neural progenitor cells (97% nestin-positive) derived from pluripotent stem cells, and MAP2-positive neurons |
| Interventions | Harmine INDY Pargyline |
| Duration | 4 days of treatment |
| Topics | Neuroplasticity |
| Key points | Harmine increased proliferation of human neural progenitor cells by 57% after 4 days and increased dendritic arborization in MAP2-positive neurons. The DYRK1A inhibitor INDY reproduced the proliferation effect while the MAO inhibitor pargyline did not, suggesting DYRK1A inhibition as a possible mechanism. The authors suggest this in vitro neurogenic activity may relate to harmine's antidepressant effects in vivo. |
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% nestinpositive) 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.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |