Indomethacin enhances learning and memory potential by interacting with CaMKII
✍ Scribed by Takeshi Kanno; Takahiro Yaguchi; Tetsu Nagata; Tadashi Shimizu; Akito Tanaka; Tomoyuki Nishizaki
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 729 KB
- Volume
- 227
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
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.