Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits

Sung Chun Tang, Thiruma V. Arumugam, Xiangru Xu, Aiwu Cheng, Mohamed R. Mughal, Gyu Jo Dong, Justin D. Lathia, Dominic A. Siler, Srinivasulu Chigurupati, Xin Ouyang, Tim Magnus, Simonetta Camandola, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We now report that neurons express several TLRs, and that the levels of TLR2 and -4 are increased in neurons in response to IFN-γ stimulation and energy deprivation. Neurons from both TLR2 knockout and -4 mutant mice were protected against energy deprivation-induced cell death, which was associated with decreased activation of a proapoptotic signaling cascade involving jun N-terminal kinase and the transcription factor AP-1. TLR2 and -4 expression was increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke were significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death.

Original languageEnglish (US)
Pages (from-to)13798-13803
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number34
DOIs
StatePublished - Aug 21 2007

Keywords

  • AP-1
  • Apoptosis
  • Innate immunity
  • Ischemic stroke
  • Microglia

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Tang, S. C., Arumugam, T. V., Xu, X., Cheng, A., Mughal, M. R., Dong, G. J., Lathia, J. D., Siler, D. A., Chigurupati, S., Ouyang, X., Magnus, T., Camandola, S., & Mattson, M. P. (2007). Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proceedings of the National Academy of Sciences of the United States of America, 104(34), 13798-13803. https://doi.org/10.1073/pnas.0702553104