Indomethacin enhances learning and memory potential by interacting with CaMKII
Indomethacin enhances learning and memory potential by interacting with CaMKII
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DOI：
10.1002/jcp.22800
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发表时间：
2012-03-01
影响因子：
5.6
通讯作者：
Nishizaki, Tomoyuki
中科院分区：
文献类型：
--
作者：
Kanno, Takeshi;Yaguchi, Takahiro;Nishizaki, Tomoyuki
本研究考察了环加氧酶抑制剂吲哚美辛（IM）对学习和记忆功能的影响。IM在培养大鼠海马神经元中激活Ca2+/钙调素依赖性蛋白激酶II （CaMKII）。IM （100 μ M）显著增加了大鼠海马CA1锥体神经元自发AMPA受体介导的微兴奋性突触后电流的速率，但不影响其振幅，并增强了细胞外高K+ (20mM)诱导的大鼠海马片谷氨酸释放，表明IM刺激突触前谷氨酸释放。这些IM效应被CaMKII抑制剂KN-93明显抑制。IM以浓度（1100 μ M）依赖的方式持续促进大鼠海马切片CA1区域的突触传递，这种方式也被KN-93消除。在水迷宫实验中，IM （1mg/kg, i.p）增强了正常大鼠的空间学习记忆能力，改善了东莨菪碱诱导的衰老加速小鼠的空间学习记忆障碍或年龄相关性空间学习记忆退化。在健康人学习由三种五位数模式组成的15个数字的测试中，口服IM （25mg/kg）显著提高了受试者在测试后5min和3天记忆的正确数字排列分数。本研究结果表明，IM在CaMKII的控制下，通过刺激突触前谷氨酸释放，促进海马突触传递，从而增强学习记忆电位。j .细胞。物理学报，27(2):998 - 996,2012。(C) 2011 Wiley期刊公司
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 mu M) 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+ (20mM)-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 (1100 mu M)-dependent manner that was also abolished by KN-93. In the water maze test, IM (1mg/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 (25mg/kg) significantly raised the scores of correct number arrangements that subjects memorized 5min 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: 919926, 2012. (C) 2011 Wiley Periodicals, Inc.