• Jinxiu Cui, Qianqian Ma, Chenxu Zhang, Yuanzhe Li, Juan Liu, Kangning Xie, Erping Luo, Mingming Zhai, and Chi Tang.
• Department of Military Medical Equipment and Metrology, School of Military Biomedical Engineering, Fourth Military Medical University, 710032 Xi'an, Shaanxi, PR China.
• Neuroscience. 2023 Mar 1; 513: 647564-75.

AbstractMemory impairment is one of the neuropsychological effects of hypobaric hypoxia (HH), which can be associated with programmed cell death, such as apoptosis and ferroptosis. Emerging evidence indicates crosstalk between apoptosis and ferroptosis, while the crosstalk between HH-induced apoptosis and ferroptosis in the hippocampus has not been clarified. Here, microarray profiles were extracted to analyze the differentially expressed genes with and without HH exposure, and keratin 18 (Krt18) was found to be a potential gene related to both apoptosis and ferroptosis. Then, we conducted morphological observations that showed that apoptosis and ferroptosis coexisted in the rat hippocampus after HH exposure. Combined with the real-time q-PCR analysis, the mRNA expression of Krt18 decreased significantly after HH exposure for 1 day and 3 days, and Mapk10 (JNK3) was upregulated at the corresponding time points. After exposure for 7 days, Krt18 and JNK3 showed no significant change. In conclusion, Krt18 may regulate apoptosis and ferroptosis simultaneously, possibly via the JNK signaling pathway, which might provide a potential central target for apoptosis and ferroptosis in hippocampal injury after HH exposure.Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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