Ferritinophagy-Mediated Hippocampus Ferroptosis is Involved in Cognitive Impairment in Immature Rats Induced by Hypoxia Combined with Propofol

作者全名："Liu, Ling; Gao, Wen; Yang, Shun; Yang, Fei; Li, Shangyingying; Tian, Yaqiong; Yang, Li; Deng, Qianyu; Gan, Zhengwei; Tu, Shengfen"

作者地址："[Liu, Ling; Gao, Wen; Yang, Shun; Yang, Fei; Li, Shangyingying; Tian, Yaqiong; Yang, Li; Deng, Qianyu; Gan, Zhengwei; Tu, Shengfen] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Anesthesiol,Childrens Hosp,Minist Educ, Key Lab Child Dev & Disorders,Chongqing Key Lab Ch, Chongqing, Peoples R China"

通信作者："Tu, SF (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Anesthesiol,Childrens Hosp,Minist Educ, Key Lab Child Dev & Disorders,Chongqing Key Lab Ch, Chongqing, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001188091800001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Ferritinophagy; Hippocampus ferroptosis; Hypoxia combined with propofol; Cognitive impairment

摘要："Propofol is a clinically common intravenous general anesthetic and is widely used for anesthesia induction, maintenance and intensive care unit (ICU) sedation in children. Hypoxemia is a common perioperative complication. In clinical work, we found that children with hypoxemia who received propofol anesthesia experienced significant postoperative cognitive changes. To explore the causes of this phenomenon, we conducted the study. In this study, our in vivo experiments found that immature rats exposed to hypoxia combined with propofol (HCWP) could develop cognitive impairment. We performed the RNA-seq analysis of its hippocampal tissues and found that autophagy and ferroptosis may play a role in our model. Next, we verified the participation of the two modes of death by detecting the expression of autophagy-related indexes Sequestosome 1 (SQSTM1) and Beclin1, and ferroptosis-related indicators Fe2+, reactive oxygen species (ROS) and glutathione peroxidase 4 (GPX4). Meanwhile, we found that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, could improve cognitive impairment in immature rats caused by HCWP. In addition, we found that nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, which acted as a key junction between autophagy and ferroptosis, was also involved. Finally, our in vitro experiments concluded that autophagy activation was an upstream factor in HCWP-induced hippocampus ferroptosis through the intervention of autophagy inhibitor 3-methyladenine (3-MA). Our study was expected to provide an attractive therapeutic target for cognitive impairment that occurred after HCWP exposures."

基金机构：Chongqing Natural Science Foundation

基金资助正文：We would like to thank Dr. Na Zang and Dr. Yuhao Wu for their help in our research ideas and analysis of sequencing results.