Ammonia-mediated LTP inhibition: Effects of NMDA receptor antagonists and L-carnitine
Ammonia-mediated LTP inhibition: Effects of NMDA receptor antagonists and L-carnitine
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DOI：
10.1016/j.nbd.2005.04.013
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Zorumski, CF
中科院分区：
文献类型：
--
作者：
Izumi, Y;Izumi, M;Zorumski, CF
由于高氨血症被认为与肝性脑病的发病机制有关，我们研究了氨对大鼠海马片中ATP水平、神经元形态和突触功能的影响。虽然氨没有改变10 mM葡萄糖支持的ATP水平，但在3.3 mM葡萄糖或10 mM丙酮酸存在下，氨显著降低了ATP水平，这表明对呼吸能量代谢的影响。氨也损害了丙酮酸维持的突触功能和神经元的完整性。在10 mM葡萄糖中，氨以浓度依赖的方式抑制长时程增强(LTP)的诱导和维持。氨的上述抑制作用可被L肉碱所克服。NMDA受体拮抗剂DL-APV也减弱了氨对ATP水平和UP诱导的影响，表明氨通过改变代谢和过早激活NMDA受体而损害神经元功能。这些结果提示，L肉碱和N-甲基-D-天冬氨酸受体拮抗剂对高氨血症时的神经元功能有保护作用。(C)2005 Elsevier Inc.保留所有权利。
Because hyperammonemia is thought to contribute to the pathogenesis of hepatic encephalopathy, we examined the effects of ammonia on ATP levels, neuronal morphology, and synaptic function in rat hippocampal slices. Although ammonia did not alter ATP levels supported by 10 mM glucose, ammonia significantly depressed ATP levels in the presence of 3.3 mM glucose or 10 mM pyruvate, suggesting effects on respiratory energy metabolism. Ammonia also impaired synaptic function and neuronal integrity sustained by pyruvate. In 10 mM glucose, ammonia inhibited the induction and maintenance of long-term potentiation (LTP) in a concentration-dependent fashion. These inhibitory effects of ammonia were overcome by L-carnitine. DL-APV, an antagonist of NMDA receptors, also diminished the effects of ammonia on ATP levels and UP induction, indicating that ammonia impairs neuronal function via altered metabolism and untimely NMDA receptor activation. These results suggest that L-carnitine and NMDA receptor antagonists have the potential to preserve neuronal function during hyperammonemia. (c) 2005 Elsevier Inc. All rights reserved.