Molecular consequences of activated microglia in the brain: Overactivation induces apoptosis

Bin Liu, Kevin Wang, Hui Ming Gao, Bhaskar Mandavilli, Jia Yi Wang, Jau Shyong Hong

研究成果: 雜誌貢獻文章

222 引文 斯高帕斯(Scopus)

摘要

Microglia, the resident immune cells in the brain, play a pivotal role in immune surveillance, host defense, and tissue repair in the CNS. In response to immunological challenges, microglia readily become activated as characterized by morphological changes, expression of surface antigens, and production of immune modulators that impact on neurons to induce neurodegeneration. However, little is known, concerning the fate of activated microglia. In the present study, stimulation of cultured rat primary microglia with 1 ng/mL of the inflammagen lipopolysaccharide (LPS) resulted in a maximal activation as measured by the release of tumor necrosis factor alpha (TNFα). However, treatment with higher concentrations of LPS resulted in significantly lower quantities of detectable TNFα. Further analysis revealed that overactivation of microglia with higher concentrations of LPS (> 1 ng/mL) resulted in a time- and dose-dependent apoptotic death of microglia as defined by DNA strand breaks, surface expression of apoptosis-specific markers (phosphatidylserine), and activation of caspase-3. In contrast, astrocytes were insensitive to LPS-induced cytotoxicity. In light of the importance of microglia and the limited replenishment mechanism, depletion of microglia from the brain may severely hamper its capacity for combating inflammatory challenges and tissue repair. Furthermore, overactivation-induced apoptosis of microglia may be a fundamental self-regulatory mechanism devised to limit bystander killing of vulnerable neurons.
原文英語
頁(從 - 到)182-189
頁數8
期刊Journal of Neurochemistry
77
發行號1
DOIs
出版狀態已發佈 - 2001
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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