Neurotoxicity and biomarkers of zinc oxide nanoparticles in main functional brain regions and dopaminergic neurons
Neurotoxicity and biomarkers of zinc oxide nanoparticles in main functional brain regions and dopaminergic neurons
复制标题
氧化锌纳米粒子在主要功能脑区和多巴胺能神经元中的神经毒性和生物标志物
DOI：
10.1016/j.scitotenv.2019.135809
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发表时间：
2020-02-25
影响因子：
9.8
通讯作者：
Xi, Zhuge
中科院分区：
文献类型：
--
作者：
Liu, Huanliang;Yang, Honglian;Xi, Zhuge
纳米氧化锌因其优异的物理化学性能在许多领域得到越来越广泛的应用。因此，生物安全已成为人类健康和环境日益关注的问题。在目前的研究中。研究了纳米氧化锌在体内和体外的神经毒性。体内实验结果表明，纳米氧化锌颗粒经鼻内滴注后易位至大脑，并在嗅球、海马、纹状体和大脑皮层沉积，引起这些部位的超微结构改变、氧化损伤、炎症反应和组织病理学损伤，这可能是纳米氧化锌神经毒性诱导的重要机制。对PC12细胞系的进一步体外研究表明，纳米氧化锌暴露6小时会影响细胞形态，降低细胞活力，增加乳酸脱氢酶和氧化应激活性水平，损害线粒体功能，扰乱细胞周期。此外，纳米氧化锌可以通过影响细胞骨架蛋白（微管蛋白- α、微管蛋白- β和NF-H）破坏神经元结构，导致神经细胞之间的连接中断，从而导致神经系统功能损伤。同时，纳米氧化锌可以通过影响钙素/钙调节激酶（CAMK2A/CAMK2B蛋白）信号通路影响生长相关蛋白GAP43，诱导神经元修复和再生障碍，并可通过影响钙素/钙调节激酶（CAMK2A/CAMK2B蛋白）信号通路诱导延迟神经毒性。(C) 2019 Elsevier B.V.版权所有
Manufactured zinc oxide nanoparticles (Nano-ZnO) are being used increasingly in many fields owing to their excellent physicochemical properties. Consequently, biosecurity has become a growing concern for human health and the environment. In the present study. Nano-ZnO neurotoxidty was investigated in vivo and in vitro. in vivo results showed that Nano-ZnO particles delivered through intranasal instillation were translocated to the brain, specifically deposited in the olfactory bulb, hippocampus, striatum, and cerebral cortex, and caused ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damages there, which may be important for inducing Nano-ZnO neurotoxidty. Further in vitro studies on PC12 cell line illustrated that exposure to Nano-ZnO for 6 h affected cell morphology, decreased cell viability, increased lactate dehydrogenase and oxidative stress activity levels, impaired mitochondrial function, and disturbed the cell cycle. In addition, Nano-ZnO could destroy neuronal structure by affecting cytoskeleton proteins (tubulin-alpha, tubulin-beta and NF-H), resulting in the interruption of connection between nerve cells, which lead to nervous system function damage. Meanwhile, Nano-ZnO could induce neuronal repair and regeneration disorders by affecting the growth-related protein GAP43 and delayed neurotoxidty by affecting the calcitun/caldum-regulated kinase (CAMK2A/CAMK2B protein) signaling pathway. (C) 2019 Elsevier B.V. All rights reserved.