LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids

Summary

LSD exposure in human cerebral organoids leads to significant changes in protein synthesis, folding, and degradation, impacting neuroplasticity and energy metabolism. The study highlights alterations in pathways related to proteostasis and cellular energy management. Additionally, LSD was shown to enhance neurite outgrowth in vitro, indicating its potential therapeutic effects on neuropsychiatric disorders.

Study at a glance

Abstract

Proteomic analysis of human cerebral organoids may reveal how psychedelics regulate biological processes, shedding light on drug-induced changes in the brain. This study elucidates the proteomic alterations induced by lysergic acid diethylamide (LSD) in human cerebral organoids. By employing high-resolution mass spectrometry-based proteomics, we quantitatively analyzed the differential abundance of proteins in cerebral organoids exposed to LSD. Our findings indicate changes in proteostasis, energy metabolism, and neuroplasticity-related pathways. Specifically, LSD exposure led to alterations in protein synthesis, folding, autophagy, and proteasomal degradation, suggesting a complex interplay in the regulation of neural cell function. Additionally, we observed modulation in glycolysis and oxidative phosphorylation, crucial for cellular energy management and synaptic function. In support of the proteomic data, complementary experiments demonstrated LSD’s potential to enhance neurite outgrowth in vitro, confirming its impact on neuroplasticity. Collectively, our results provide a comprehensive insight into the molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.