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

Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento, Ivan Domith, Karina Karmirian, Amanda Feilding, Pablo Trindade, Daniel Martins-de-Souza, Stevens K. Rehen

ACS Omega August 27, 2024 DOI: 10.1021/acsomega.4c04712 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational study Peer reviewed
Population Human cerebral organoids
Intervention LSD
Topics LSD Neuroplasticity
Keywords Mental health Drug effects Psychedelics Brain research
Citations 3
Key findings LSD exposure alters proteins involved in proteostasis, energy metabolism, and neuroplasticity-related pathways in human cerebral organoids.

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.

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