Indomethacin enhances learning and memory potential by interacting with CaMKII

• Published in: Journal of cellular physiology Vol. 227; no. 3; pp. 919 - 926
• Main Authors: Kanno, Takeshi, Yaguchi, Takahiro, Nagata, Tetsu, Shimizu, Tadashi, Tanaka, Akito, Nishizaki, Tomoyuki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2012
• Subjects: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cells, Cultured; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Female; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - enzymology; Hippocampus - pathology; Humans; Indomethacin - administration & dosage; Indomethacin - metabolism; Indomethacin - pharmacology; Male; Maze Learning - drug effects; Maze Learning - physiology; Memory - drug effects; Memory - physiology; Mice; Middle Aged; Neurons - drug effects; Neurons - enzymology; Neurons - pathology; Organ Culture Techniques; Rats; Rats, Wistar; Xenopus; Young Adult
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.22800

The present study examined the effect of indomethacin (IM), a cyclooxygenase inhibitor, on learning and memory functions. IM activated Ca2+/calmodulin‐dependent protein kinase II (CaMKII) in cultured rat hippocampal neurons. IM (100 µM) significantly increased the rate of spontaneous AMPA receptor‐mediated miniature excitatory postsynaptic currents elicited from CA1 pyramidal neurons of rat hippocampal slices, without affecting the amplitude, and enhanced extracellular high K+ (20 mM)‐induced glutamate release from rat hippocampal slices, indicating that IM stimulates presynaptic glutamate release. Those IM effects were clearly inhibited by the CaMKII inhibitor KN‐93. IM persistently facilitated synaptic transmission monitored from the CA1 region of rat hippocampal slices in a concentration (1–100 µM)‐dependent manner that was also abolished by KN‐93. In the water maze test, IM (1 mg/kg, i.p.) enhanced spatial learning and memory ability for normal rats, and ameliorated scopolamine‐induced spatial learning and memory impairment or age‐related spatial learning and memory deterioration for senescence‐accelerated mouse‐prone 8 mice. In the test to learn 15 numbers consisting of three patterns of five digit number for healthy human subjects, oral intake with IM (25 mg/kg) significantly raised the scores of correct number arrangements that subjects memorized 5 min and 3 days after the test. The results of the present study indicate that IM could enhance learning and memory potential by facilitating hippocampal synaptic transmission as a result from stimulating presynaptic glutamate release under the control of CaMKII. J. Cell. Physiol. 227: 919–926, 2012. © 2011 Wiley Periodicals, Inc.