Year: 2025
Type: article
Abstract: Major depressive disorder (MDD) is a debilitating psychiatric condition associated with substantial personal, societal, and economic costs. Despite considerable advances in research, most conventional antidepressant therapies fail to achieve adequate response in a significant proportion of patients, underscoring the need for novel, mechanism-based interventions. Lycium barbarum glycopeptide (LbGp), a bioactive compound with emerging neuroprotective properties, has been proposed as a candidate for antidepressant development; however, its therapeutic efficacy and underlying mechanisms remain largely uncharacterized. In this study, ventral forebrain organoids were generated from patients with MDD to investigate disease-related neurophysiological abnormalities. These organoids exhibited disrupted neuronal morphology, diminished calcium signaling, and impaired electrophysiological activity. Administration of LbGp effectively restored structural and functional deficits in MDD-derived organoids. Transcriptomic profiling revealed that LbGp ameliorated endoplasmic reticulum (ER) stress responses. To investigate the causative role of ER stress, control organoids were treated with the ER stress agonist CCT020312, which elicited neural activity impairments resembling those observed in MDD organoids. Notably, LbGp reversed the phenotypic consequences of CCT020312 exposure in control organoids. In conclusion, ventral forebrain organoids derived from individuals with MDD demonstrated that LbGp ameliorates disease-associated phenotypes by modulating ER stress.
Source: 动物学研究
Authors: Tao Meng-Dan, 南京医科大学药学院干细胞与神经再生研究所, 江苏 南京 211166, 中国, Wang Can, Wu Xin-Hao, Chen Qi, Gao Wei-Wei, Xu Min, Hong Yuan, Han Xiao, Zhu Wan-Ying, Zhu Qian, Liu Yan, Guo Xing, 南京医科大学生殖医学国家重点实验室, 江苏 南京 211166, 中国, 南京医科大学基础医学院神经生物学系, 江苏 南京 211166, 中国, 南京医科大学第二附属医院, 江苏 南京 210011, 中国
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4411918166