AMPA receptor activation reduces epileptiform activity in the rat neocortex
AMPA receptor activation reduces epileptiform activity in the rat neocortex
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DOI：
10.1016/j.brainres.2007.05.002
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发表时间：
2007-07-16
期刊：
影响因子：
2.9
通讯作者：
Stone, Trevor W.
中科院分区：
文献类型：
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作者：
Addae, Jonas I.;Ali, Nakisha;Stone, Trevor W.
我们之前报道过，将α -氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）局部应用于大鼠新皮层可以防止随后应用n -甲基- d -天冬氨酸（NMDA）的作用。NMDA受体的激活参与了癫痫活动的发病机制。因此，我们研究了局部应用AMPA是否会影响双核碱引起的体感诱发电位（sep）和皮质电图（ECoG）癫痫峰的变化。AMPA （50 μ M）对癫痫样活动的抑制作用与地西泮（3 mg/kg .p）或氯咪唑（100 mg/kg .p）相当。此外，AMPAR拮抗剂CNQX或AMPAR脱敏阻滞剂环噻嗪也能抑制癫痫样活性。在海马体切片中，从CA1细胞记录到的包括双核素在内的群体尖峰电位的变化不受AMPA的影响。我们得出结论，在大鼠新皮层的复杂神经元网络中，可以通过多种针对AMPA受体的策略来抑制癫痫样活动：(1)阻断AMPA受体，(2)促进AMPA受体的明显脱敏（可能在锥体神经元上）或(3)减少AMPA受体的明显脱敏（可能在抑制性gaba能中间神经元上）。(c) 2007 Elsevier B.V.版权所有
We have previously reported that topical application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects of a subsequent application of N-methyl-D-aspartic acid (NMDA). Activation of NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore, we examined if topically applied AMPA could affect changes in the somatosensory evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by bicuculline. AMPA (50 mu M) prevented the epileptiform activity to a level that was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100 mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. in the hippocampal slice, bicuculline-incluced changes in the population spike potentials recorded from the CA1 cells were not affected by AMPA. We conclude that in the complex neuronal network of the rat neocortex, epileptiform activity can be suppressed in a variety of strategies that target the AMPA receptors: (1) blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA receptors (possibly on the pyramidal neurons) or (3) reducing an apparent desensitization of AMPA receptors (possibly on the inhibitory GABAergic interneurons). (c) 2007 Elsevier B.V. All rights reserved.