title: Active calcium/calmodulin-dependent protein kinase II (CaMKII) regulates NMDA receptor mediated postischemic long-term potentiation (i-LTP) by promoting the interaction between CaMKII and NMDA receptors in ischemia.
abstract: Active calcium/calmodulin-dependent protein kinase II (CaMKII) has been reported to take a critical role in the induction of long-term potentiation (LTP). Changes in CaMKII activity were detected in various ischemia models. It is tempting to know whether and how CaMKII takes a role in NMDA receptor (NMDAR)-mediated postischemic long-term potentiation (NMDA i-LTP). Here, we monitored changes in NMDAR-mediated field excitatory postsynaptic potentials (NMDA fEPSPs) at different time points following ischemia onset in vitro oxygen and glucose deprivation (OGD) ischemia model. We found that 10 min OGD treatment induced significant i-LTP in NMDA fEPSPs, whereas shorter (3 min) or longer (25 min) OGD treatment failed to induce prominent NMDA i-LTP. CaMKII activity or CaMKII autophosphorylation displays a similar bifurcated trend at different time points following onset of ischemia both in vitro OGD or in vivo photothrombotic lesion (PT) models, suggesting a correlation of increased CaMKII activity or CaMKII autophosphorylation with NMDA i-LTP. Disturbing the association between CaMKII and GluN2B subunit of NMDARs with short cell-permeable peptides Tat-GluN2B reversed NMDA i-LTP induced by OGD treatment. The results provide support to a notion that increased interaction between NMDAR and CaMKII following ischemia-induced increased CaMKII activity and autophosphorylation is essential for induction of NMDA i-LTP.
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, China.
authors.forename: Ning
authors.identifier: 0000-0002-4327-8331
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, China.
authors.forename: Nan
authors.identifier: 0000-0003-2756-0764
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing, China ; Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000503:physiopathology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D020767:Intracranial Thrombosis / Q000473:pathology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005947:Glucose
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