The Ayahuasca’s psychedelic component DMT potentiates neuritogenesis in PC12 cells

Ayahuasca is a psychedelic beverage originally from the Amazon rainforest used in different shamanic settings for a variety of medicinal, spiritual, and cultural purposes. It is prepared by decoction of the vine Banisteriopsis caapi, source of β-carboline alkaloids, and, Psychotria viridis containing the classic psychedelic N,N-dimethyltryptamine (DMT). As part of the “renaissance of psychedelic studies”, several recent reports highlight its potential therapeutic applications for the treatment of depression and substance use disorders, among others. The DMT present in Ayahuasca is a potent agonist of the serotoninergic receptor 5-HT2A, interacts with other serotonin receptors, the sigma-1 receptor and trace amine-associated receptor 1 (TAAR1). DMT has been recently categorized as a “psychoplastogen”, able to promote structural and functional neuroplastic changes in cortical cell cultures. This property suggests that the therapeutic potential of DMT might include other pathologies where neuronal plasticity is compromised like in neurodegenerative diseases. In this work, we studied DMT’s ability to promote neuritogenesis in the catecholaminergic cell line PC12. When cultured in the presence of nerve growth factor (NGF), PC12 cells differentiate and acquire neuronal characteristics both morphologically and functionally. We used PC12 cells as a model to characterize DMT’s ability to promote neuritogénesis by itself and under NGF deficient conditions, as a potential treatment for neurodegeneration of catecholaminergic systems. Percentage of cells that developed neurites was determined by manually counting previously MTT-dyed and fixed treated PC12 cells. We used pharmacological inhibitors to characterize the molecular mechanisms involved. We have found that DMT promotes neuritogenesis in PC12 cells by itself and potentiates NGF-mediated neurite outgrowth under NGF-deficient conditions. We are now working on the elucidation of the molecular pathways involved in this novel activity using pharmacological inhibitors of the Akt, Erk and PLCg pathways, and 5-HT2A receptor inhibitor. Preliminary results suggest the involvement of Akt pathway in such effect.

Agencia Nacional de Investigación e Innovación

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