کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6259844 | 1290010 | 2011 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research reportNMDA preconditioning protects against quinolinic acid-induced seizures via PKA, PI3K and MAPK/ERK signaling pathways Research reportNMDA preconditioning protects against quinolinic acid-induced seizures via PKA, PI3K and MAPK/ERK signaling pathways](/preview/png/6259844.png)
Preconditioning by N-methyl-d-aspartate (NMDA) may be promoted in vivo by the administration of a sub-convulsing dose of NMDA, with a neuroprotective effect against seizures and neuronal death induced by the infusion of quinolinic acid (QA) in mice. This study aimed to evaluate the participation of protein kinase C (PKC), cyclic AMP-dependent protein kinase (PKA), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK), Ca2+/calmodulin dependent protein kinase II (CaMKII) and phosphatidilinositol-3 kinase (PI3K) signaling pathways in this neuroprotection model. Adult Swiss male mice were preconditioned with NMDA 24Â h before the infusion of QA, and were treated with inhibitors of the aforementioned signaling pathways either 15Â min before the preconditioning or infusion of QA. Inhibition of the PKA and PI3K pathways abolished the protection evoked by NMDA, and inhibition of the MEK pathway significantly diminished this protection. Treatment with PKC and CaMKII inhibitors did not alter the protection rate. Inhibition of the MEK and PKC pathways resulted in an increased mortality rate when followed by the infusion of QA, or NMDA preconditioning and QA infusion, respectively. These results suggest that the PKA, PI3K and MEK pathways have a crucial role in the achievement of a neuroprotective state following preconditioning.
Research highlightsⶠNMDA preconditioning in vivo is neuroprotective against seizures induced by i.c.v. infusion of quinolinic acid in mice. ⶠAdministration of PKA or PI3K pathways inhibitors completely abolished the protection evoked by NMDA. ⶠInhibition of the MEK pathway significantly diminished the NMDA-induced protection. ⶠTreatment with PKC or CaMKII inhibitors did not alter the NMDA protection rate. ⶠInhibition of the MEK or PKC pathways resulted in an increased mortality rate after quinolinic acid infusion.
Journal: Behavioural Brain Research - Volume 219, Issue 1, 16 May 2011, Pages 92-97