Evaluating the implication of silica nanoparticles in neurodegeneration

Abstract

Silica nanoparticles (SiO2-NPs) are typical and major components of mineral dust and many other airborne pollutants in the ambient air. Although evidence shows that nano-sized particles may have neurotoxicity and induce neuroinflammation. Whether exposure to SiO2-NPs results in neurodegenerative-like behavioral and pathological changes is not known. In this study, we employed fluorescein isothiocyanate-tagged SiO2-NPs (FITC-SiO2-NPs, NPs) to investigate the effects of SiO2-NPs on affective and cognitive behaviors in mice. Effects of NPs on synapse were studied in primary culture of cortical neurons and mice. We exposed 3-month-old male C57BL/6N mice to NPs suspension through intranasal instillation, and subjected the mice to a battery of behavior tests after 1 or 2 months treatment. We found that NPs decreased social activity, 2-month treatment-induced anxiety, and impaired memory in novel object recognition test and spatial learning and memory in Morris water maze test. We found deposition of NPs in the medial prefrontal cortex and the hippocampus. Meanwhile, we found neurodegenerative-like pathological changes in the frontal cortex, including reduction in Nissl bodies, increased phosphorylation of tau, and neuroinflammation. In both frontal cortex synaptosome and primary culture of cortical neurons, we found impairment in exocytosis function, accompanied with a decrease of synapsin I and an increase of synaptophysin. Taken together, intranasal instillation of NPs results in mood dysfunction and cognitive impairment in mice, and it may attribute to the neurodegenerative-like pathological and synaptic changes.