N Costa Marcelo, Goto-Silva Livia, M Nascimento Juliana, Domith Ivan, Karmirian Karina, Feilding Amanda, Trindade Pablo, Martins-de-Souza Daniel, K Rehen Stevens
D'Or Institute for Research and Education, Rua Diniz Cordeiro, 30-Botafogo, Rio de Janeiro 22281-100, RJ, Brazil.
Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373 - Cidade Universitária, Rio de Janeiro 21941-902, RJ, Brazil.
ACS Omega. 2024 Aug 16;9(34):36553-36568. doi: 10.1021/acsomega.4c04712. eCollection 2024 Aug 27.
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 , 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.
对人类大脑类器官的蛋白质组学分析可能会揭示迷幻药如何调节生物过程，从而阐明药物引起的大脑变化。本研究阐明了麦角酸二乙酰胺（LSD）在人类大脑类器官中诱导的蛋白质组学改变。通过采用基于高分辨率质谱的蛋白质组学技术，我们定量分析了暴露于LSD的大脑类器官中蛋白质的差异丰度。我们的研究结果表明蛋白质稳态、能量代谢和神经可塑性相关途径发生了变化。具体而言，LSD暴露导致蛋白质合成、折叠、自噬和蛋白酶体降解发生改变，这表明在神经细胞功能调节中存在复杂的相互作用。此外，我们观察到糖酵解和氧化磷酸化的调节，这对细胞能量管理和突触功能至关重要。作为对蛋白质组学数据的支持，补充实验证明了LSD增强神经突生长的潜力，证实了其对神经可塑性的影响。总的来说，我们的结果全面深入地了解了LSD可能影响神经可塑性并可能有助于治疗神经精神疾病的分子机制。
