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Indomethacin enhances learning and memory potential by interacting with CaMKII
Author(s) -
Kanno Takeshi,
Yaguchi Takahiro,
Nagata Tetsu,
Shimizu Tadashi,
Tanaka Akito,
Nishizaki Tomoyuki
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22800
Subject(s) - hippocampal formation , excitatory postsynaptic potential , hippocampus , neuroscience , glutamate receptor , neurotransmission , nmda receptor , ampa receptor , postsynaptic potential , chemistry , extracellular , endocrinology , biology , receptor , inhibitory postsynaptic potential , biochemistry
The present study examined the effect of indomethacin (IM), a cyclooxygenase inhibitor, on learning and memory functions. IM activated Ca 2+ /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.