title: Neurotoxicity of silica nanoparticles: brain localization and dopaminergic neurons damage pathways.
abstract: Silica nanoparticles (SiO(2)-NPs) are being used increasingly in diagnosis, imaging, and drug delivery for the central nervous system. However, to date, little is known concerning the potential adverse effects on the brain associated with exposure to SiO(2)-NPs. The present study was conducted to trace, locate, and quantify SiO(2)-NPs in the brain by a radiolabeling approach after intranasal instillation with SiO(2)-NPs. The oxidative stress, inflammatory response, and levels of neurochemicals in the brain were also analyzed. Furthermore, in vitro studies were carried out to elucidate the pathway and mechanism of in vivo damage with a co-incubation model of dopaminergic neuron PC12 and SiO(2)-NPs. The results indicated that SiO(2)-NPs via intranasal instillation entered into the brain and especially deposited in the striatum. Exposure to SiO(2)-NPs also induced oxidative damage and an increased inflammatory response in the striatum. Meanwhile, results of in vitro studies demonstrated that exposure to SiO(2)-NPs decreased cell viability, increased levels of lactate dehydrogenase, triggered oxidative stress, disturbed cell cycle, induced apoptosis, and activated the p53-mediated signaling pathway. In addition, the in vivo injury of neurochemicals occurred as the SiO(2)-NPs appeared to induce depleted dopamine in the striatum, and the down-regulation of tyrosine hydroxylase protein was the main contribution. These data demonstrate that SiO(2)-NPs possibly have a negative impact on the striatum and dopaminergic neurons as well as a potential risk for neurodegenerative diseases. There is potential concern with SiO(2)-NPs' neurotoxicity in biomedical applications and occupational exposure in large-scale production.
authors.affiliation: Shanghai Biomaterials Research & Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D016503:Drug Delivery Systems; D007249:Inflammation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine