多巴胺在聚(I:C)诱导的神经炎症过程中的电化学动态探测

IF 13 2区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Small Pub Date : 2024-11-20 DOI:10.1002/smll.202407685
Jian Wang, Qiang Zhou, Yuchan Zhang, Shuang Zhao, Li Li, Zhongyuan Zeng, Jiajia Chen, Yangmingxu Meng, Xianglong Zhao, Tianqi Wang, Zexuan Meng, Haihan Yuan, Jianhua Ran, Guixue Wang, Chen-zhong Li, Guangchao Zang
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引用次数: 0

摘要

病毒可侵入中枢神经系统并导致抑郁症,其中可能包括由免疫反应引发的多巴胺(DA)代谢的改变,但其中涉及的具体机制仍不清楚。本文提出了一种实现高灵敏度多巴胺实时动态监测的电化学系统,并通过单纳米线、碳纤维(CF)和二维柔性电极等多尺度电极的组合,证明病毒模拟物聚肌苷酸(poly(I:C))能从单细胞、细胞群甚至体内的角度抑制神经元中多巴胺的释放(从 5.595 微米到 0.137 微米)。这些发现与小胶质细胞产生的活性氧(ROS)增加有关。在分子水平上,poly(I:C)能显著降低α-突触核蛋白的表达并增加其磷酸化水平,而ROS抑制剂能逆转这些病理变化,并将DA释放量恢复到初始水平的一半(≈2.6 µM)。这些结果表明,病毒可能会通过炎症反应中产生的 ROS 间接抑制 DA 系统的功能,而抗氧化活性可能是一种潜在的治疗策略。
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Electrochemical Probing of Dopamine Dynamics During Poly(I:C)-Induced Neuroinflammation
Viruses can infiltrate the central nervous system and contribute to depression, which may include alterations in dopamine (DA) metabolism triggered by immune responses though the specific mechanisms involved remain unclear. Here, an electrochemical system to realize the real-time dynamic monitoring of DA with high sensitivity is proposed and it is demonstrated that the viral simulator polyinosinic-polycytidylic acid (poly(I:C)) can inhibit the release of DA (from 5.595 to 0.137 µm) in neurons from the perspective of single cells, cell populations and even in vivo through the combination of multiscale electrodes, including single nanowires, carbon fibers (CFs) and 2D flexible electrodes. These findings are associated with the increase in reactive oxygen species (ROS) produced by microglia. At the molecular level, poly(I:C) significantly decreases the expression of α-synuclein and increases its phosphorylation level, whereas ROS inhibitors can reverse these pathological changes and salvage DA release to half the initial level (≈2.6 µM). These results suggest that viruses may indirectly inhibit DA system function through ROS produced in inflammatory responses and that antioxidant activity may be a potential therapeutic strategy.
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来源期刊
Small
Small 工程技术-材料科学:综合
CiteScore
17.70
自引率
3.80%
发文量
1830
审稿时长
2.1 months
期刊介绍: Small serves as an exceptional platform for both experimental and theoretical studies in fundamental and applied interdisciplinary research at the nano- and microscale. The journal offers a compelling mix of peer-reviewed Research Articles, Reviews, Perspectives, and Comments. With a remarkable 2022 Journal Impact Factor of 13.3 (Journal Citation Reports from Clarivate Analytics, 2023), Small remains among the top multidisciplinary journals, covering a wide range of topics at the interface of materials science, chemistry, physics, engineering, medicine, and biology. Small's readership includes biochemists, biologists, biomedical scientists, chemists, engineers, information technologists, materials scientists, physicists, and theoreticians alike.
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