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 A40 secretion in the culture medium with
ALT cells and N2a cells, and attenuated gene expressions of Aclearance 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 Ageneration. 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.