The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition
The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition
复制标题
阿司匹林代谢物水杨酸盐通过减少 GABA 能抑制增强大鼠海马 CA1 区神经元兴奋
DOI：
10.1016/j.neuropharm.2007.10.017
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发表时间：
2008-02-01
影响因子：
4.7
通讯作者：
Xu, Tian-Le
中科院分区：
文献类型：
--
作者：
Gong, Neng;Zhang, Min;Xu, Tian-Le
水杨酸盐是阿司匹林(乙酰水杨酸)的主要代谢物和活性成分，广泛用于临床治疗炎症、疼痛综合征和心血管疾病。众所周知，水杨酸盐的作用机制主要包括抑制环氧合酶和随后减少前列腺素的产生。最近的证据表明，水杨酸盐也通过与特定的膜通道/受体相互作用而影响神经元的功能。然而，水杨酸盐对突触和神经网络功能的影响在很大程度上仍不清楚。在本研究中，我们研究了水杨酸钠对大鼠海马CA1区突触传递和神经元兴奋的影响，CA1区是许多复杂脑功能的关键结构。在海马片的电生理记录中，我们发现水杨酸钠通过减少抑制性GABA能传递而不影响基础兴奋性突触传递而显著增强神经元的兴奋。水杨酸盐显著抑制大鼠海马神经元诱发的突触后电流和微小的抑制性突触后电流的幅度，并直接降低GABA(A)受体介导的反应。综上所述，我们的结果表明，广泛使用的阿司匹林可能通过对GABA能神经传递的作用而损害海马区突触和神经网络功能。鉴于阿司匹林能够穿透血脑屏障，目前的数据表明，服用阿司匹林可能会导致网络性多动，并对易感人群造成潜在危害。(C)2007爱思唯尔有限公司。保留所有权利。
Salicylate is the major metabolite and active component of aspirin (acetylsalicylic acid), which is widely used in clinical medicine for treating inflammation, pain syndromes and cardiovascular disorders. The well-known mechanism underlying salicylate's action mainly involves the inhibition of cyclooxygenase and subsequent decrease in prostaglandin production. Recent evidence suggests that salicylate also affects neuronal function through interaction with specific membrane channels/receptors. However, the effect of salicylate on synaptic and neural network function remains largely unknown. In this study, we investigated the effect of sodium salicylate on the synaptic transmission and neuronal excitation in the hippocampal CA1 area of rats, a key structure for many complex brain functions. With electrophysiological recordings in hippocampal slices, we found that sodium salicylate significantly enhanced neuronal excitation through reducing inhibitory GABAergic transmission without affecting the basal excitatory synaptic transmission. Salicylate significantly inhibited the amplitudes of both evoked and miniature inhibitory postsynaptic currents, and directly reduced gamma-aminobutyric acid type A (GABA(A)) receptor-mediated responses in cultured rat hippocampal neurons. Together, our results suggest that the widely used aspirin might impair hippocampal synaptic and neural network functions through its actions on GABAergic neurotransmission. Given the capability of aspirin to penetrate the blood-brain barrier, the present data imply that aspirin intake may cause network hyperactivity and be potentially harmful in susceptible subpopulations. (C) 2007 Elsevier Ltd. All rights reserved.