Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons
OpenAlex – June 07, 2024
Source: OpenAlex
Summary
Psilocin, psilocybin's active form, dramatically enhances neuroplasticity in human cortical neurons derived from stem cells. Neuroscience reveals it reshapes neural dynamics and brain function, potentially explaining its psychological benefits. Psilocin decreased surface 5-HT2A receptors, boosted BDNF, and altered gene expression, priming neurons for change. Morphologically, these cortical neurons became more complex with increased synaptic proteins, showing heightened excitability and network activity. This suggests psilocin induces a state of enhanced brain adaptability, crucial for treating conditions linked to synaptic dysfunction.
Abstract
Abstract Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from induced pluripotent stem cells with the 5-HT2A receptor agonist psilocin - the psychoactive metabolite of psilocybin. We analyzed how exposure to psilocin affects 5-HT2A receptor localization, gene expression, neuronal morphology, synaptic markers and neuronal function. Upon exposure of human neurons to psilocin, we observed a decrease of cell surface-located 5-HT2A receptors first in the axonal- followed by the somatodendritic-compartment. Psilocin further provoked a 5-HT2A-R-mediated augmentation of BDNF abundance. Transcriptomic profiling identified gene expression signatures priming neurons to neuroplasticity. On a morphological level, psilocin induced enhanced neuronal complexity and increased expression of synaptic proteins, in particular in the postsynaptic-compartment. Consistently, we observed an increased excitability and enhanced synaptic network activity in neurons treated with psilocin. In conclusion, exposure of human neurons to psilocin might induces a state of enhanced neuronal plasticity which could explain why psilocin is beneficial in the treatment of neuropsychiatric disorders where synaptic dysfunctions are discussed.