• Ruixi Zhou, Xuemei Sun, Yuyao Li, Qun Huang, Yi Qu, Dezhi Mu, and Xihong Li.
• Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China.
• Neuroscience. 2019 Nov 1; 419: 83-99.

AbstractStudies have shown that a certain dose of dexamethasone can improve the survival rate of patients with sepsis, and in sepsis associated encephalopathy (SAE), autophagy plays a regulatory role in brain function. Here, we proved for the first time that small-dose dexamethasone (SdDex) can regulate the autophagy of cerebral cortex neurons in SAE rats and plays a protective role. Cortical neurons were cultured in vitro in a septic microenvironment and a sepsis rat model was established. The small-dose dexamethasone (SdDex) or high-dose dexamethasone (HdDex) was used to intervene in neurons or SAE rats. Through fluorescence microscopy and western blot analysis, the expressions of microtubule-associated protein 1 light chain 3 (LC3), p62/sequestosome1 (p62/SQSTM1), mammalian target of rapamycin (mTOR) signaling pathway related proteins, and apoptosis-related proteins were detected. Theresultsshowthat compared with those in SAE rats, the cortical pathological changes in SAE rats treated with SdDex were improved, and damaged substances were encapsulated and degraded by autophagosomes in neurons. Additionally, similar to neurons in vitro, cortical autophagy was further activated and the mTOR signaling pathway was inhibited. After HdDex treatment, the mTOR signaling pathway in cortex is inhibited, but further activation of autophagy is not obvious, the cortical pathological changes were further worsened and the ultrastructure of neurons was disturbed. Furthermore, the HdDex group exhibited the most obvious apoptosis. SdDex can regulate autophagy of cortical neurons by inhibiting the mTOR signaling pathway and plays a protective role. Brain damage induced by HdDex may be related to the activation of apoptosis.Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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