Prostaglandin E2 Type 1 Receptors Contribute to Neuronal Apoptosis after Transient Forebrain Ischemia. Issue 8 (August 2013)

• Record Type: Journal Article
• Authors: Shimamura, Munehisa; Zhou, Ping; Casolla, Barbara; Qian, Liping; Capone, Carmen; Kurinami, Hitomi; ladecola, Costantino; Anrather, Josef
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 33:Issue 8(2013)
• Page Start: 1207
• Page End: 1214
• Publication Date: 2013-08
• Subjects: AKT -- apoptosis -- calcineurin -- cerebral ischemia -- cyclooxygenase -- prostaglandin E2; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2013.69
• Languages: English
• ISSNs: 0271-678X

Abstract

Cyclooxygenase-2-derived prostaglandin E2 (PGE2 ) contributes to excitotoxic and ischemic neuronal cell death by engaging neuronal PGE2 type 1 receptors (EP1R). Our previous studies have shown that EP1R signaling resulted in disturbances of intracellular Ca 2 + homeostasis and suppression of the pro-survival protein kinase AKT. The aim of this study was to investigate whether these pathophysiological mechanism have a role in the neuronal cell death after transient forebrain ischemia. Mice were subjected to ischemia/reperfusion by bilateral common carotid artery occlusion. Hippocampal cornu ammonis area 1 (CA1) neuronal cell death was determined 5 days after reperfusion. Animals treated with the EP1R antagonist SC51089 or EP1R-deficient mice (EP1 –/– ) showed significantly less neuronal injury as compared to vehicle-treated wild-type controls. Benefits of EP1R blockage were still evident 14 days after injury. Better neuronal survival was correlated with reduced neuronal caspase-3 activity and decreased nuclear translocation of the apoptosis-inducing factor. Neuroprotection could be reverted by intracerebroventricular administration of the phosphoinositide 3-kinase inhibitor LY294002 and was not further increased by the calcineurin inhibitor FK506. These data implicate EP1R in postischemic neuronal apoptosis possibly by facilitating AKT inhibition.