Impact of silica nanoparticles-induced neurodegeneration and cognitive impairment, an example on the effect of environmental pollutant

Abstract

Silica nanoparticles(SiO2-NPs) are one of the most broadly exploited nanomaterials and have been utilized in a variety of industries. They are also the most common component in a number of airborne pollutants, including mineral dust and particulate matter (PM),found in ambient air as well as circulated air in households and workplaces. Air pollution has been considered to be a risk factor for inducing Alzheimer’s disease (AD). After inhalation, SiO2-NPs penetrate the epithelium of the respiratory tract and are then translocated to the brain via either the circulatory system or the olfactory nerve. However, the role of SiO2-NPs in neurodegeneration is largely unknown. Here, we evaluated the effects of SiO2-NPs-exposure on behavior, neuropathology, and synapse in young adult mice and primary cortical neuron cultures. Male C57BL/6N mice (3 months old) were exposed to either vehicle (sterile PBS) or fluorescein isothiocyanate-tagged SiO2-NPs (NP) using intranasal instillation. Behavioral tests were performed after 1 and 2 months of exposure. We observed decreased social activity at both time points as well as anxiety and cognitive impairment after 2 months in the NP-exposed mice. NP deposition was primarily detected in the medial prefrontal cortex and the hippocampus. Neurodegeneration-like pathological changes, including reduced Nissl bodies, increased tau phosphorylation, and neuroinflammation, were also present in the brains of NP-exposed mice. Furthermore, we observed NP-induced impairment in exocytosis along with decreased synapsin I and increased synaptophysin expression in the synaptosome fractions isolated from the frontal cortex as well as primary neuronal cultures. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were also activated in the frontal cortex of NP-exposed mice. Moreover, inhibition of ERK activation prevented NP-mediated changes in exocytosis in cultured neurons, highlighting a key role in the changes induced by NP exposure. In conclusion, intranasal instillation of SiO2-NPs results in mood dysfunction and cognitive impairment in young adult mice and causes neurodegeneration-like pathology and synaptic changes via ERK activation. The results may explain why air pollution can be a risk factor for developing AD.