Oldenziel W H, Dijkstra G, Cremers T I F H, Westerink B H C
Department of Biomonitoring and Sensoring, University Center for Pharmacy, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Brain Res. 2006 Nov 6;1118(1):34-42. doi: 10.1016/j.brainres.2006.08.015. Epub 2006 Sep 7.
Recent discoveries have revealed that glutamatergic neurotransmission in the central nervous system is mediated by a dynamic interplay between neurons and astrocytes. To enhance our understanding of this process, the study of extracellular glutamate is crucial. At present, microdialysis is the most frequently used analytical technique to monitor extracellular glutamate levels directly in the brain. However, the neuronal and physiological origin of the detected glutamate levels is questioned as they do not fulfil the classical release criteria for exocytotic release, such as calcium dependency or response to the sodium channel blocker tetrodotoxine (TTX). It is hypothesized that an analytical technique with a higher spatial and temporal resolution is required. Glutamate microsensors provide a promising analytical solution to meet this requirement. In the present study, we applied a 10 micro m diameter hydrogel-coated glutamate microsensor to monitor extracellular glutamate levels in the striatum of anesthetized rats. To explore the potential of the microsensor, different pharmacological agents were injected in the vicinity of the sensor at an approximate distance of 100 micro m. It was observed that KCl, exogenous glutamate, kainate and the reuptake inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) increased the extracellular glutamate levels significantly. TTX decreased the basal extracellular glutamate levels approximately 90%, which indicates that the microsensor is capable of detecting neuronally derived glutamate. This is one of the first studies in which a microsensor is applied in vivo on a routine base, and it is concluded that microsensor research can contribute significantly to improve our understanding of the physiology of glutamatergic neurotransmission in the brain.
最近的研究发现，中枢神经系统中的谷氨酸能神经传递是由神经元和星形胶质细胞之间的动态相互作用介导的。为了加深我们对这一过程的理解，研究细胞外谷氨酸至关重要。目前，微透析是最常用的直接监测大脑中细胞外谷氨酸水平的分析技术。然而，检测到的谷氨酸水平的神经元和生理来源受到质疑，因为它们不符合经典的胞吐释放标准，如钙依赖性或对钠通道阻滞剂河豚毒素（TTX）的反应。据推测，需要一种具有更高空间和时间分辨率的分析技术。谷氨酸微传感器为满足这一要求提供了一种有前景的分析解决方案。在本研究中，我们应用直径为10微米的水凝胶包被的谷氨酸微传感器来监测麻醉大鼠纹状体中的细胞外谷氨酸水平。为了探索微传感器的潜力，在距离传感器约100微米的附近注射了不同的药理学试剂。观察到氯化钾、外源性谷氨酸、海人酸和再摄取抑制剂DL-苏式-β-苄氧基天冬氨酸（DL-TBOA）显著提高了细胞外谷氨酸水平。TTX使基础细胞外谷氨酸水平降低了约90%，这表明微传感器能够检测神经元来源的谷氨酸。这是首次在体内常规应用微传感器的研究之一，得出的结论是，微传感器研究可以显著有助于提高我们对大脑中谷氨酸能神经传递生理学的理解。
