S100A8 regulates autophagy-dependent ferroptosis in microglia after experimental subarachnoid hemorrhage

Qianke Tao; Xiancheng Qiu; Chaojie Li; Jian Zhou; Long Gu; Lihan Zhang; Jinwei Pang; Lifang Zhang; Shigang Yin; Yong Jiang; Jianhua Peng

doi:10.1016/j.expneurol.2022.114171

S100A8 regulates autophagy-dependent ferroptosis in microglia after experimental subarachnoid hemorrhage

Exp Neurol. 2022 Nov:357:114171. doi: 10.1016/j.expneurol.2022.114171. Epub 2022 Jul 21.

Authors

Qianke Tao¹, Xiancheng Qiu¹, Chaojie Li¹, Jian Zhou², Long Gu³, Lihan Zhang¹, Jinwei Pang², Lifang Zhang³, Shigang Yin⁴, Yong Jiang⁵, Jianhua Peng⁶

Affiliations

¹ Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
² Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Sichuan Clinical Research Center for Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
³ Sichuan Clinical Research Center for Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
⁴ Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou 646000, China; Academician (Expert) Workstation of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: sgyin@swmu.edu.cn.
⁵ Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou 646000, China; Academician (Expert) Workstation of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: jiangyong@swmu.edu.cn.
⁶ Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Laboratory of Neurological Diseases and Brain Function, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Institute of Epigenetics and Brain Science, Southwest Medical University, Luzhou 646000, China; Academician (Expert) Workstation of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: pengjianhua@swmu.edu.cn.

PMID: 35870523
DOI: 10.1016/j.expneurol.2022.114171

Abstract

Targeting microglial activation has been shown to ameliorate early brain injury (EBI) after subarachnoid hemorrhage (SAH). Ferroptosis is a new form of programmed cell death after SAH, but these molecular features were not recognized as evidence of microglial function so far. In this study, we constructed microglial S100A8-specific knockdown and established the SAH model in vivo and in vitro. Multi-technology strategies, including high throughput sequencing, adeno-associated virus gene gene-editing and several molecular biotechnologies to validate the effects of S100A8 on microglial autophagy and ferroptosis after SAH. Our results revealed that the expression of S100A8 was significantly increased in brain tissue after SAH. Targeted microglial S100A8 inhibition improved neural function and neuronal apoptosis in mice after SAH. Further mechanism exploration found that favourable effects of S100A8 depletion in EBI may be through the inhibition of microglia autophagy-dependent ferroptosis. In conclusion, S100A8 may be a potential intervention target for microglial ferroptosis in EBI after SAH.

Keywords: Autophagy; Ferroptosis; Microglia; S100A8; Subarachnoid hemorrhage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy
Brain Injuries* / metabolism
Ferroptosis*
Mice
Microglia / metabolism
Subarachnoid Hemorrhage* / metabolism