title: Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits.
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-gamma 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.
authors: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
authors: Sung-Chun
authors: SC
authors: Tang
authors: Thiruma V
authors: TV
authors: Arumugam
authors: Xiangru
authors: X
authors: Xu
authors: Aiwu
authors: A
authors: Cheng
authors: Mohamed R
authors: MR
authors: Mughal
authors: Dong Gyu
authors: DG
authors: Jo
authors: Justin D
authors: JD
authors: Lathia
authors: Dominic A
authors: DA
authors: Siler
authors: Srinivasulu
authors: S
authors: Chigurupati
authors: Xin
authors: X
authors: Ouyang
authors: Tim
authors: T
authors: Magnus
authors: Simonetta
authors: S
authors: Camandola
authors: Mark P
authors: MP
authors: Mattson
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007371:Interferon-gamma / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3
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