Obstructive Sleep Apnea Plasma-Derived Exosomes Mediate Cognitive Impairment Through Hippocampal Neuronal Cell Pyroptosis

• Published in: The American journal of geriatric psychiatry 2024-08, Vol.32 (8), p.922-939
• Main Authors: Chen, Zhifeng, Shang, Yulin, Ou, Yanru, Shen, Chong, Cao, Ying, Hu, Hui, Yang, Ruibing, Liu, Ting, Liu, Qingqing, Song, Min, Zong, Dandan, Xiang, Xudong, Peng, Yating, Ouyang, Ruoyun
• Format: Article
• Language: English
• Subjects: Animals; Case-Control Studies; Caspase 1 - metabolism; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; cognitive impairment; exosome; Exosomes - metabolism; Female; Gasdermins; GSDMD; Hippocampus - metabolism; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Male; Mice; Mice, Inbred C57BL; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neurons - metabolism; OSA; Phosphate-Binding Proteins - metabolism; Pyroptosis - physiology; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - metabolism; Sleep Apnea, Obstructive - physiopathology
• ISSN: 1064-7481; 1545-7214; 1545-7214
• DOI: 10.1016/j.jagp.2024.01.017

•What is the primary question addressed by this study? The question addressed by the study must limited to only one sentence?The aim of this study was to investigate whether OSA plasma-derived exosomes cause cognitive impairment through hippocampal neuronal pyroptosis, and to identify differential expression of exosome miRNAs in OSA plasma-derived.•What is the main finding of this study? The finding must be limited to two sentences?The results of this study showed for the first time that plasma exosomes from severe OSA patients can promote pyroptosis in vivo and in vitro, increase the expression of inflammatory factors, and lead to impaired cognitive function in mice, and there are differentially expressed miRNAs of exosomes from OSA plasma-derived.•What is the meaning of the finding? The meaning of the finding must be limited to one sentence?The meaning of this study proves that OSA plasma-derived exosomes mediate OSA-related cognitive impairment through pyroptosis, providing new insights into the pathogenesis and treatment of cognitive impairment complicated by OSA. Obstructive sleep apnea (OSA) is associated with impaired cognitive function. Exosomes are secreted by most cells and play a role in OSA-associated cognitive impairment (CI). The aim of this study was to investigate whether OSA plasma-derived exosomes cause CI through hippocampal neuronal cell pyroptosis, and to identify exosomal miRNAs in OSA plasma-derived. Plasma-derived exosomes were isolated from patients with severe OSA and healthy comparisons. Daytime sleepiness and cognitive function were assessed using the Epworth Sleepiness Scale (ESS) and the Beijing version of the Montreal Cognitive Assessment Scale (MoCA). Exosomes were coincubated with mouse hippocampal neurons (HT22) cells to evaluate the effect of exosomes on pyroptosis and inflammation of HT22 cells. Meanwhile, exosomes were injected into C57BL/6 male mice via caudal vein, and then morris water maze was used to evaluate the spatial learning and memory ability of the mice, so as to observe the effects of exosomes on the cognitive function of the mice. Western blot and qRT-PCR were used to detect the expressions of Gasdermin D (GSDMD) and Caspase-1 to evaluate the pyroptosis level. The expression of IL-1β, IL-6, IL-18 and TNF-α was detected by qRT-PCR to assess the level of inflammation. Correlations of GSDMD and Caspase-1 expression with clinical parameters were evaluated using Spearman's rank correlation analysis. In addition