altered mrna editing and expression of ionotropic glutamate receptors after kainic acid exposure in cyclooxygenase-2 deficient mice改变信使rna编辑和ionotropic谷氨酸受体的表达在cyclooxygenase-2海人酸接触后缺陷的老鼠.pdfVIP

Altered mRNA Editing and Expression of Ionotropic Glutamate Receptors after Kainic Acid Exposure in Cyclooxygenase-2 Deficient Mice 1,2 2 1 2 1 Luca Caracciolo , Alessandro Barbon , Sara Palumbo , Cristina Mora , Christopher D. Toscano , 1 ¤ 2 Francesca Bosetti * , Sergio Barlati 1 Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy Abstract Kainic acid (KA) binds to the AMPA/KA receptors and induces seizures that result in inflammation, oxidative damage and neuronal death. We previously showed that cyclooxygenase-2 deficient (COX-22/ 2) mice are more vulnerable to KA-induced excitotoxicity. Here, we investigated whether the increased susceptibility of COX-22/ 2 mice to KA is associated with altered mRNA expression and editing of glutamate receptors. The expression of AMPA GluR2, GluR3 and KA GluR6 was increased in vehicle-injected COX-22/ 2 mice compared to wild type (WT) mice in hippocampus and cortex, whereas gene expression of NMDA receptors was decreased. KA treatment decreased the expression of AMPA, KA and NMDA receptors in the hippocampus, with a significant effect in COX-22/ 2 mice. Furthermore, we analyzed RNA editing levels and found that the level of GluR3 R/G editing site was selectively increased in the hippocampus and decreased in the cortex in COX-22/ 2 compared with WT mice. After KA, GluR4 R/G editing site, flip form, was increa