Gong Neng, Zhang Min, Zhang Xiao-Bing, Chen Lin, Sun Guang-Chun, Xu Tian-Le
Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Neuropharmacology. 2008 Feb;54(2):454-63. doi: 10.1016/j.neuropharm.2007.10.017. Epub 2007 Nov 6.
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.
水杨酸酯是阿司匹林（乙酰水杨酸）的主要代谢产物和活性成分，阿司匹林在临床医学中广泛用于治疗炎症、疼痛综合征和心血管疾病。水杨酸酯作用的著名机制主要涉及抑制环氧化酶以及随后前列腺素生成的减少。最近的证据表明，水杨酸酯还通过与特定膜通道/受体相互作用来影响神经元功能。然而，水杨酸酯对突触和神经网络功能的影响在很大程度上仍然未知。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性的影响，海马CA1区是许多复杂脑功能的关键结构。通过对海马切片进行电生理记录，我们发现水杨酸钠通过减少抑制性GABA能传递而显著增强神经元兴奋性，而不影响基础兴奋性突触传递。水杨酸酯显著抑制诱发的和微小的抑制性突触后电流的幅度，并直接降低培养的大鼠海马神经元中A型γ-氨基丁酸（GABA(A)）受体介导的反应。总之，我们的结果表明，广泛使用的阿司匹林可能通过其对GABA能神经传递的作用损害海马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，摄入阿司匹林可能会导致网络活动亢进，并对易感亚群有潜在危害。
