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

Abstract
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.


Author - Chun-Yu Chuang, Ho-Chen Lin, Ming-Yi Ho

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| Published on 2017-06-28
   
   
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