MK-801 and 7-Ni attenuate the activation of brain NF-κB induced by LPS

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• 作者：Glezer ; Isaias ; Munhoz ; Carolina Demarchi ; Kawamoto ; Elisa Mitiko ; Marcourakis ; Tania ; Avellar ; Maria Christina Werneck ; et. al.
• 关键词：Glutamate ; N-methyl-d-aspartate ; Neuroinflammation ; NF-κ ; B ; Nitric oxide ; LPS
• 刊名：Neuropharmacology
• 出版年：2003
• 出版时间：December, 2003
• 年：2003
• 卷：45
• 期：8
• 页码：1120-1129
• 全文大小：495 K

文摘

The activation of nuclear factor-κB (NF-κB) leads to an increase in the expression of genes involved in important events in the central nervous system (CNS), such as development, plasticity and inflammation. It has been shown that inflammatory stimulus in the brain increases excitatory glutamatergic transmission, especially at N-methyl-d-aspartate (NMDA) receptor. These receptors have an important role in glutamate neurotoxicity and are in general coupled with the generation of nitric oxide (NO) through the activation of neuronal nitric oxide synthase (NOS). We have investigated the involvement of NMDA–NO pathway in LPS induction of NF-κB in CNS. Our results demonstrate that systemic LPS activates NF-κB in several regions of the CNS, which was partially reduced by the NMDA receptor antagonist dizolcipine (MK-801) and by the selective brain NOS inhibitor 7-Nitroindazol (7-Ni). 7-Ni effects were not synergic to MK-801 effects, suggesting that these compounds act through the same pathway. Dexamethasone caused a stronger reduction in LPS induction of NF-κB in CNS, demonstrating that MK-801 and 7-Ni act on a pathway that is responsible only by a fraction of the overall NF-κB activation. These results suggest that a considerable part of NF-κB activation by LPS is linked to the NMDA/NO pathway in CNS.