Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release

Ge Gao, Congcong Li, Jie Zhu, Yi Wang, Yunlong Huang, Shu Zhao, Shiyang Sheng, Yu Song, Chenhui Ji, Chunhong Li, Xiaoyu Yang, Ling Ye, Xinrui Qi, Yanyan Zhang, Xiaohuan Xia, Jialin C. Zheng

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Cerebral ischemia induces a robust neuroinflammatory response that is largely mediated by the activation of CNS resident microglia. Activated microglia produce pro-inflammatory molecules to cause neuronal damage. Identifying regulators of microglial activation bears great potential in discovering promising candidates for neuroprotection post cerebral ischemia. Previous studies demonstrate abnormal elevation of glutaminase 1 (GLS1) in microglia in chronic CNS disorders including Alzheimer's disease and HIV-associated neurocognitive disorders. Ectopic expression of GLS1 induced microglia polarization into pro-inflammatory phenotype and exosome release in vitro. However, whether GLS1 is involved in neuroinflammation in acute brain injury remains unknown. Here, we observed activation of microglia, elevation of GLS1 expression, and accumulation of pro-inflammatory exosomes in rat brains 72 h post focal cerebral ischemia. Treatment with CB839, a glutaminase inhibitor, reversed ischemia-induced microglial activation, inflammatory response, and exosome release. Furthermore, we found that the application of exosome secretion inhibitor, GW4869, displayed similar anti-inflammatory effects to that of CB839, suggesting GLS1-mediated exosome release may play an important role in the formation of neuroinflammatory microenvironment. Therefore, GLS1 may serve as a key mediator and promising target of neuroinflammatory response in cerebral ischemia.

Original languageEnglish (US)
Article number161
JournalFrontiers in immunology
Volume11
DOIs
StatePublished - Feb 7 2020

Keywords

  • brain inflammation
  • exosome
  • focal cerebral ischemia
  • glutaminase 1
  • glutaminase inhibitor
  • microglial activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release'. Together they form a unique fingerprint.

Cite this