title: Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus.
abstract: The phosphorylation of calcium/calmodulin-dependent protein kinase (CaMK) II, induced by an increase in the intracellular Ca2+ concentration, is involved in the alteration of brain functions such as memory formation. In the present study, we examined the influence of various immobilization stress paradigms on the phosphorylation of CaMKII (phospho-CaMKII) and CaMKII levels in the rat hippocampus. Immunoblot and immunohistochemical analyses were performed to examine the levels of CaMKII and phospho-CaMKII. Real-time quantitative polymerase chain reaction (PCR) was performed to analyse the mRNA levels of N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes. Acute (single) and repeated (4 d), but not chronic (14 d), stress exposure of 45 min or longer duration significantly increased phospho-CaMKII levels without affecting the levels of CaMKII. Pre-treatment with NBQX, a selective AMPA receptor antagonist, significantly prevented this stress-induced increase. In contrast, two NMDA receptor antagonists, LY235959 and MK-801, showed no inhibitory effect on phospho-CaMKII levels during acute stress. Neither acute nor chronic stress changed mRNA levels of NMDA and AMPA receptors. These results demonstrate that immobilization stress promotes the phosphorylation of CaMKII. The increase in the intracellular Ca2+ concentration by the activation of AMPA receptors may play a role in the stress-induced phospho-CaMKII in the rat hippocampus.
authors.affiliation: Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Suenaga
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Ki-Ichiro
authors.initials: K
authors.lastname: Kawano
authors.forename: Takuya
authors.initials: T
authors.lastname: Sawada
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017931:DNA Primers; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000201:enzymology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D017931:DNA Primers; D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D007546:Isoquinolines; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009553:Nimodipine; D016291:Dizocilpine Maleate; C088643:LY 235959; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases