Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, People's Republic of China.
Int J Nanomedicine. 2020 Jun 19;15:4407-4415. doi: 10.2147/IJN.S254480. eCollection 2020.
Silica nanoparticles (SiO NPs) have been extensively employed in biomedical field. SiO NPs are primarily designed to enter the circulatory system; however, little information is available on potential adverse effects of SiO NPs on the nervous system.
The neurotoxicity of SiO NPs at different concentrations (3, 6, 12 ng/nL) on zebrafish embryos was determined using immunofluorescence and microarray techniques, and subsequently confirmed by qRT-PCR.
SiO NPs disrupt the axonal integrity and decrease the length of axons in Tg (NBT: EGFP) transgenic lines. The number of apoptotic cells in the brain and central nervous system of zebrafish embryos was increased in the presence of 12 ng/nL of SiO NPs, but the difference did not reach statistical significance. Screening for changes in the expression of genes involved in the neuroactive ligand-receptor interaction pathway was performed by microarray and confirmed by qRT-PCR. These analyses demonstrated that SiO NPs markedly downregulated genes associated with neural function (grm6a, drd1b, chrnb3b, adrb2a, grin2ab, npffr2.1, npy8br, gabrd, chrma3, gabrg3, gria3a, grm1a, adra2b, and glra3).
The obtained results documented that SiO NPs can induce developmental neurotoxicity by affecting the neuroactive ligand-receptor interaction signaling pathway. This new evidence may help to clarify the mechanism of SiO NPs-mediated neurotoxicity.
二氧化硅纳米颗粒（SiO NPs）已广泛应用于生物医学领域。SiO NPs 的设计初衷是进入循环系统；然而，关于 SiO NPs 对神经系统潜在的不良影响的信息却很少。
采用免疫荧光和微阵列技术，确定了不同浓度（3、6、12ng/nL）SiO NPs 对斑马鱼胚胎的神经毒性，并通过 qRT-PCR 进行了后续验证。
SiO NPs 破坏了 Tg（NBT：EGFP）转基因系轴突的完整性，降低了轴突的长度。在 12ng/nL SiO NPs 存在的情况下，斑马鱼胚胎大脑和中枢神经系统中的凋亡细胞数量增加，但差异没有达到统计学意义。通过微阵列筛选参与神经活性配体-受体相互作用途径的基因表达变化，并通过 qRT-PCR 进行了验证。这些分析表明，SiO NPs 显著下调了与神经功能相关的基因（grm6a、drd1b、chrnb3b、adrb2a、grin2ab、npffr2.1、npy8br、gabrd、chrma3、gabrg3、gria3a、grm1a、adra2b 和 glra3）。
研究结果表明，SiO NPs 可通过影响神经活性配体-受体相互作用信号通路，诱导发育性神经毒性。这一新证据可能有助于阐明 SiO NPs 介导的神经毒性的机制。
