Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210, USA.
Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Angew Chem Int Ed Engl. 2023 Oct 16;62(42):e202310245. doi: 10.1002/anie.202310245. Epub 2023 Sep 13.
Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 μm, can detect real-time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.
中枢神经系统中的化学生物标志物可以提供有价值的定量测量方法，深入了解神经疾病的病因和发病机制。谷氨酸是大脑中最重要的兴奋性神经递质之一，已在各种神经疾病中发现其表达上调，如创伤性脑损伤、阿尔茨海默病、中风、癫痫、慢性疼痛和偏头痛。然而，定量监测原位谷氨酸释放一直具有挑战性。这项工作提出了一类新型的柔性、小型化探针，灵感来自生物燃料电池，用于监测神经系统中突触释放的谷氨酸。这些传感器的尺寸低至 50×50μm，可以检测到生物相关浓度范围内谷氨酸的实时变化。利用小鼠模型中的海马回路进行的实验证明了传感器通过急性脑切片使用电刺激监测谷氨酸释放的能力。这些进展可以帮助基础神经科学研究和转化工程，因为传感器为神经疾病提供了一种诊断工具。此外，通过将生物燃料电池设计适应于其他神经递质，可以潜在地实现对神经递质失调对神经元细胞信号通路影响的详细研究，并彻底改变神经科学。
