Harmine, substance in ayahuasca brew promotes neural progenitor cell proliferation.

Ayahuasca is a beverage that has been used for centuries by Native South-Americans. Studies suggest that it exhibits anxiolytic and antidepressant effects in humans. One of the main substances present in the beverage is harmine, a beta-carboline which potential therapeutic effects for depression has been recently described in mice.

“It has been shown in rodents that antidepressant medication acts by inducing neurogenesis. So we decided to test if harmine, an alkaloid with the highest concentration in the psychotropic plant decoction ayahuasca, would trigger neurogenesis in human neural cells”, said Vanja Dakic, PhD student and one of the authors in the study.

In order to elucidate these effects, researchers from the D’Or Institute for Research and Education (IDOR) and the Institute of Biomedical Sciences at the Federal University of Rio de Janeiro (ICB-UFRJ) exposed human neural progenitors to this beta-carboline. After four days, harmine led to a 70% increase in proliferation of human neural progenitor cells.

Researchers were also able to identify how the human neural cells respond to harmine. The described effect involves the inhibition of DYRK1A, which is located on chromosome 21 and is over-activated in patients with Down syndrome and Alzheimer’s Disease.

“Our results demonstrate that harmine is able to generate new human neural cells, similarly to the effects of classical antidepressant drugs, which frequently are followed by diverse side effects. Moreover, the observation that harmine inhibits DYRK1A in neural cells allows us to speculate about future studies to test its potential therapeutic role over cognitive deficits observed in Down syndrome and neurodegenerative diseases”, suggests Stevens Rehen, researcher from IDOR and ICB-UFRJ.

Citation: “Harmine stimulates proliferation of human neural progenitors.” Vanja Dakic, Renata de Moraes Maciel, Hannah Drummond, Juliana M. Nascimento, Pablo Trindade & Stevens K. Rehen. PeerJ 2016 vol: 4 pp: e2727.
DOI: 10.7717/peerj.2727
Research funding: Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico
Adapted from press release by D’Or Institute for Research and Education.

Transplantation with induced neural stem cells (iNSC) improves stroke recovery in mice

In a study to determine whether induced neural stem cells (iNSCs), a type of somatic cell directly differentiated into neural stem cells, could exert therapeutic effects when transplanted into mice modeled with ischemic stroke, researchers found that the cells promoted survival and functional recovery. Additionally, they discovered that when administered during the acute phase of stroke, iNSCs protected the brain from ischemia-related damage.

In contrast to other studies that have induced somatic cells to become pluripotent stem cells (iPSCs), which can then be differentiated into neural cells, this study directly converted somatic cells into neural stem cells. Researchers concluded that in addition to iNSC transplantation improving survival rate, results also demonstrated reduced infarct volume in the brain and enhanced sensorimotor function in the mice modeled with stroke. The study will be published in a future issue of Cell Transplantation.

“We observed multiple therapeutic effects when using these cells to treat stroke in mice,” said Dr. Koji Abe, Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science. “The iNSCs did not produce any adverse responses in the animals, including tumor formation, which may suggest they are safer than regular iPSCs. Further studies are needed to confirm this cell type as a candidate for cell replacement therapy for stroke.”

“Use of iNSCs may improve the efficacy of cell transplantation procedures for stroke since they are able to be derived directly from other cells without the need for extra steps,” said Dr. Shinn-Zong (John) Lin, Tzu Chi Hospital, Hualien City, Taiwan. “This is highly desirable in stroke, which has a narrow window in which the brain is most responsive to treatment. Whether the therapeutic effects produced by iNSCs are attributable to cell replacement or to secreted factors (paracrine effects), this method may be promising for treating stroke early.”

Publication: Novel therapeutic transplantation of induced neural stem cells for stroke.
DOI: http://dx.doi.org/10.3727/096368916X692988
Adapted from press release by Cell Transplantation