Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus.
Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus.
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外周限制的病毒攻击会升高细胞外谷氨酸并增强海马体中的突触传递。
DOI：
10.1111/jnc.13665
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发表时间：
2016
影响因子：
4.7
通讯作者：
Reed,MirandaN
中科院分区：
文献类型：
--
作者：
Hunsberger,HollyC;Wang,Desheng;Petrisko,TiffanyJ;Alhowail,Ahmad;Setti,SharayE;Suppiramaniam,Vishnu;Konat,GregoryW;Reed,MirandaN
外周感染增加了易感人群癫痫发作的倾向和严重程度。我们先前已经证明，腹腔注射一种病毒模拟物，多肌苷多胞酸(PIC)，可以引起小鼠对红藻氨酸(KA)诱导的癫痫的过敏反应。这项研究是为了确定这种癫痫过敏反应是否会导致谷氨酸信号的改变。给雌性C57BL/6小鼠腹腔注射PIC，24小时后，用酶基微电极阵列监测海马区谷氨酸稳态。PIC刺激可显著提高细胞外静息谷氨酸水平。突触前钾诱导的谷氨酸释放不受影响，谷氨酸摄取严重受损，非囊泡性谷氨酸释放增加，提示星形胶质细胞功能改变。来自PIC挑战的小鼠的海马片的电生理学检查显示，与对照组相比，基础突触传递增加了几倍。PIC刺激也增加了突触前谷氨酸释放的可能性，从双脉冲易化和突触可塑性的减少可以看出，从长时程增强的增强可以看到。总之，我们的结果提示星形胶质细胞谷氨酸代谢的失调和兴奋性突触传递的改变是导致海马区高兴奋性发展的潜在机制，从而导致外周PIC挑战后的癫痫过敏。外周感染/炎症增加了癫痫的易感性。在这里，我们探讨了由病毒模拟物引起的腹膜炎症对小鼠海马区谷氨酸稳态和谷氨酸能神经传递的影响。我们发现，腹膜炎症增加了细胞外谷氨酸浓度，增加了突触前谷氨酸释放的可能性，从而导致神经元网络的过度兴奋。这些机制很可能是癫痫发作倾向增强的基础。
Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal injection of a viral mimic, polyinosinic‐polycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)‐induced seizures. This study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were intraperitoneally injected with PIC, and after 24 h, glutamate homeostasis in the hippocampus was monitored using the enzyme‐based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While pre‐synaptic potassium‐evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non‐vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC‐challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of pre‐synaptic glutamate release as seen from a reduction of paired‐pulse facilitation and synaptic plasticity as seen from an enhancement of long‐term potentiation. Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge.Peripheral infections/inflammations enhance seizure susceptibility. Here, we explored the effect of peritoneal inflammation induced by a viral mimic on glutamate homeostasis and glutamatergic neurotransmission in the mouse hippocampus. We found that peritoneal inflammation elevated extracellular glutamate concentration and enhanced the probability of pre‐synaptic glutamate release resulting in hyperexcitability of neuronal networks. These mechanisms are likely to underlie the enhanced seizure propensity.