Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus

• Published in: The international journal of neuropsychopharmacology 2004-09, Vol.7 (3), p.299-309
• Main Authors: Suenaga, Takami, Morinobu, Shigeru, Kawano, Ki-ichiro, Sawada, Takuya, Yamawaki, Shigeto
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Calcium Channel Blockers; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Dizocilpine Maleate - pharmacology; DNA Primers; Excitatory Amino Acid Antagonists - pharmacology; Hippocampus - enzymology; Immunohistochemistry; Isoenzymes - metabolism; Isoquinolines - pharmacology; Male; Nimodipine - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Restraint, Physical; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - physiology; Stress, Psychological - enzymology; Up-Regulation - physiology
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145704004304

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 α-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.