Nanoparticles (NPs) can be transported to the brain, especially through nerves, because of their small size and high biological activity. Previous studies confirmed that zinc oxide (ZnO) NPs can enter the brain through the tongue-brain pathway, but it is unclear whether they will further affect synaptic transmission and brain perception. In this study, it is found that tongue-brain-transported ZnO NPs can cause a decrease in taste sensitivity and taste aversion learning ability, indicating abnormal taste perception. Moreover, the release of miniature excitatory postsynaptic currents, the frequency of action potential release, and the expression of c-fos are decreased, suggesting that the synaptic transmission is reduced. To further explore the mechanism, protein chip detection of inflammatory factors is carried out and it is found that neuroinflammation occurs. Importantly, it is found that neuroinflammation originated from neurons. The JAK-STAT signaling pathway is activated, which inhibits the Neurexin1-PSD95-Neurologigin1 pathway and c-fos expression. Blocking the activation of the JAK-STAT pathway prevents neuroinflammation and the reduction in Neurexin1-PSD95-Neurologigin1. These results indicate that ZnO NPs can be transported by the tongue-brain pathway and lead to abnormal taste perception by neuroinflammation-induced deficits in synaptic transmission. The study reveals the influence of ZnO NPs on neuronal function and provides a novel mechanism.
Keywords: nanoparticles; nerve transport; neuroinflammation; synaptic transmission; taste.
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