Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway.

Autor: Li D; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Xu N; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Hou Y; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Ren W; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Zhang N; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Wang X; Yantai Affiliated Hospital of Binzhou Medical University, 717 Jinbu Street, YanTai, 264199, China., Sun Y; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Lu W; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Qu G; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China., Yu Y; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China. yuyan405@aliyun.com., Lv C; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China. luckylcj@aliyun.com., Han F; Binzhou Medical University, 346 Guanhai Road, YanTai, 264003, China. hanfangtuandui@aliyun.com.
Jazyk: angličtina
Zdroj: Molecular medicine (Cambridge, Mass.) [Mol Med] 2022 Jan 14; Vol. 28 (1), pp. 3. Date of Electronic Publication: 2022 Jan 14.
DOI: 10.1186/s10020-021-00427-8
Abstrakt: The mechanisms of chronic intermittent hypoxia (CIH)-induced cognitive deficits remain unclear. Here, our study found that about 3 months CIH treatment induced lipid droplets (LDs) accumulation in hippocampal nerve and glia cells of C57BL/6 mice, and caused severe neuro damage including neuron lesions, neuroblast (NB) apoptosis and abnormal glial activation. Studies have shown that the neuronal metabolism disorders might contribute to the CIH induced-hippocampal impairment. Mechanistically, the results showed that pyruvate dehydrogenase complex E1ɑ subunit (PDHA1) and the pyruvate dehydrogenase complex (PDC) activator pyruvate dehydrogenase phosphatase 1 (PDP1) did not noticeable change after intermittent hypoxia. Consistent with those results, the level of Acetyl-CoA in hippocampus did not significantly change after CIH exposure. Interestingly, we found that CIH produced large quantities of ROS, which activated the JNK/SREBP/ACC pathway in nerve and glia cells. ACC catalyzed the carboxylation of Acetyl-CoA to malonyl-CoA and then more lipid acids were synthesized, which finally caused aberrant LDs accumulation. Therefore, the JNK/SREBP/ACC pathway played a crucial role in the cognitive deficits caused by LDs accumulation after CIH exposure. Additionally, LDs were peroxidized by the high level of ROS under CIH conditions. Together, lipid metabolic disorders contributed to nerve and glia cells damage, which ultimately caused behavioral dysfunction. An active component of Salvia miltiorrhiza, SMND-309, dramatically alleviated these injuries and improved cognitive deficits of CIH mice.
(© 2022. The Author(s).)
Databáze: MEDLINE
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