The role of ferroptosis in chronic intermittent hypoxia-induced cognitive impairment

作者全名："Liu, Zhi-li; Huang, Yin-pei; Wang, Xin; He, Yu-xin; Li, Juan; Li, Bing"

作者地址："[Liu, Zhi-li; Huang, Yin-pei; Wang, Xin; He, Yu-xin; Li, Juan; Li, Bing] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Li, J; Li, B (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：SLEEP AND BREATHING

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000909908200001

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：　

期号：　

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结束页：　

文献类型：Article; Early Access

关键词：Obstructive sleep apnea; Cognitive impairment; Chronic intermittent hypoxia; Ferroptosis

摘要："Purpose Obstructive sleep apnea (OSA) is a sleep disorder that may lead to cognitive impairment. The primary pathophysiological feature of OSA is chronic intermittent hypoxia (CIH), but the underlying mechanisms of CIH are not known. There have been few studies on the role of ferroptosis, a novel form of programmed cell death, during CIH-induced cognitive impairment. Therefore, this paper examined ferroptosis' effect on CIH-mediated cognitive impairment. Methods The study randomized twenty-four Sprague-Dawley (SD) male rats to control or CIH group. CIH rats were subjected to intermittent hypoxia for 4 weeks. Rat learning and memory were analyzed by the Morris water maze (MWM) test. Alterations of hippocampal neuronal ultrastructure were observed by transmission electron microscopy (TEM). Malondialdehyde (MDA) and ferrous iron (Fe2+) levels and superoxide dismutase (SOD) and reduced glutathione (GSH) contents were determined. Ferroptosis-associated protein levels were examined by Western blotting. Results The MWM test indicated that rats in the CIH group exhibited neurocognitive impairment. TEM showed that CIH induced mitochondrial damage. Significant increases in Fe2+ and MDA levels were observed in the CIH group, and GSH and SOD levels were decreased. Expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) increased, and glutathione peroxidase 4 (GPX4) protein levels were decreased, suggesting that ferroptosis was induced in CIH model rats. The NF-E2-related factor 2 (Nrf2) protein level in the CIH group was decreased. Conclusion Ferroptosis had an essential effect on CIH-mediated cognitive impairment, and it may occur via Nrf2 dysregulation. These findings lay a solid foundation for the subsequent study of OSA-associated cognitive impairment offering potential evidence for the development of therapeutic strategies."

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