Paper Title
Neurodegenerative Effect of Exposure to Silver Nanoparticles in Mouse in Vitro Blood-Brain Barrier Model

Silver nanoparticles (AgNPs) are widely used in daily supplies. AgNPs can induce inflammatory response in neuronal cells, and potentially develop neurological disorders. This study used transcriptomic gene-network and proteomic analysis to investigate the neurodegenerative effect of exposure to silver nanoparticles in mouse in-vitro blood-brain barrier model. A triple cell co-culture model constructed of mouse endothelial bEnd.3 cells, astrocyte ALT cells and neuronal N2a cells was used to explore whether AgNPs (3-5 nm) could disrupt tight junction proteins of endothelial cells and alter gene expression and proteomic metabolism of neuronal cells for amyloid beta (A) deposition underlying Alzheimer’s disease (AD) progression. AgNPs exposure disrupted tight junction proteins, increased amyloid precursor protein (APP) formation, and gene expressions of A generation secretases, presenilin 1 (PSEN1), PSEN2 and􀀀􀀀-site of amyloid precursor protein cleaving enzyme (BACE), for APP cleavage in ALT cells and N2a cells, stimulated A40 secretion in the culture medium with ALT cells and N2a cells, and attenuated gene expressions of A􀀀clearance receptors, p-glycoprotein (p-gp) and low density lipoprotein receptor-related protein 1 (LRP-1), in bEnd.3 cells. AgNPs-induced palmitic acid was detected in N2a cells, which might promote A􀀀generation. These findings of this study suggested that AgNPs exposure might alter gene expression and protein metabolism to cause A􀀀 deposition for neuronal apoptosis potentially for the development of AD progression. Index Terms- silver nanoparticles, transcriptomic gene-network, proteomic analysis, blood brain barrier, tight junction protein, amyloid beta clearance, Alzheimer’s disease.