Abstract
BackgroundThe extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known.MethodsIn this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro.ResultsThis analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca2+-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level.ConclusionThis study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis.
Highlights
The extensive biological applications of zinc oxide nanoparticles (ZnO Zinc oxide nanoparticles (NPs)) in stomatology have created serious concerns about their biotoxicity
We demonstrated that zinc oxide nanoparticles (ZnO NPs) and titanium dioxide NPs (TiO2 NPs) can be taken up by taste buds and translocated into the brain via taste nerves (chorda tympani (CT) and glossopharyngeal nerves), providing a new pathway for NPs to translocate into the brain [15]
Neurodegeneration disturbs the properties of the central nervous system (CNS) and affects neuronal function, which is associated with many neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal lobar dementia (FTLD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS)
Summary
The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. Large numbers of studies have shown that intranasal instillation of nanoparticles can be transported along the olfactory nerve and trigeminal nerve into CNS, resulting in neurotoxicity [11,12,13,14]. Nanoparticles tongue instillation is likely to be uptaken by taste bud cells and transported into CNS via the taste nerve pathway. NPs deposited onto the brain induce oxidative damage and degenerate learning and memory, resulting in neurodegeneration. The neurodegeneration caused by tongue-instilled ZnO NPs and TiO2 NPs may be associated with neuroinflammation. This study aimed to investigate whether tongue-instilled ZnO NPs induce inflammatory responses in the CNS and to evaluate the potential molecular mechanisms underlying this process
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