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通过氧化还原状态和氧化应激的协同管理对神经元进行调节

Neuron Modulation by Synergetic Management of Redox Status and Oxidative Stress.

作者信息

Liu Xianping, Jiang Xingwu, Liu Zonghao, Chen Feixiang, Chen Jian, Chu Xu, Bu Wenbo, Liu Yanyan

机构信息

Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Academy for Engineering and Technology, Fudan University, Shanghai, 200433, P. R. China.

出版信息

Small. 2025 Feb;21(8):e2408494. doi: 10.1002/smll.202408494. Epub 2025 Jan 24.

DOI:10.1002/smll.202408494
PMID:39853947
Abstract

The transient receptor potential (TRP) channel is a key sensor for diverse cellular stimuli, regulating the excitability of primary nociceptive neurons. Sensitization of the TRP channel can heighten pain sensitivity to innocuous or mildly noxious stimuli. Here, reversible modulation of TRP channels is achieved by controlling both the light-induced photoelectrochemical reaction to induce neuronal depolarization, and antioxidants for neuronal protection. It is based on a hybrid nanosystem, CZPN, created by coating CeO nanocrystals with the metalloporphyrin ZnTPyP. Light irradiation triggers an electrochemical response, with efficient electron injection from ZnTPyP to CeO, converting Ce into Ce as antioxidants. Meanwhile, the charge migrates from surrounding O molecules to the hole-injected ZnTPyP, giving rise to reactive oxygen species (ROS). This change in the redox environment sensitizes TRP channels, eliciting action potentials in primary rat neurons, and is partially blocked by pretreatment with capsazepine. The resulting CeO, with a high Ce/Ce ratio, can scavenge excessive ROS to prevent oxidative damage. The light-induced pain behaviors in mice pre-injected with CZPN are further confirmed. This work suggests a safe, effective, and universal approach to photoelectrochemical processes for modulation and research of the peripheral nervous system.

摘要

瞬时受体电位(TRP)通道是多种细胞刺激的关键传感器,可调节初级伤害性神经元的兴奋性。TRP通道的敏化可增强对无害或轻度有害刺激的疼痛敏感性。在此,通过控制光诱导的光电化学反应以诱导神经元去极化以及使用抗氧化剂进行神经元保护,实现了对TRP通道的可逆调节。它基于一种混合纳米系统CZPN,该系统通过用金属卟啉ZnTPyP包覆CeO纳米晶体而制成。光照射引发电化学反应,电子从ZnTPyP高效注入到CeO中,将Ce转化为Ce作为抗氧化剂。同时,电荷从周围的O分子迁移到注入空穴的ZnTPyP,产生活性氧(ROS)。氧化还原环境的这种变化使TRP通道敏化,在原代大鼠神经元中引发动作电位,并且在用辣椒素预处理后会部分被阻断。所产生的具有高Ce/Ce比率的CeO可以清除过量的ROS以防止氧化损伤。预先注射CZPN的小鼠中光诱导的疼痛行为得到了进一步证实。这项工作为外周神经系统的调节和研究提供了一种安全、有效且通用的光电化学过程方法。

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