Do Silver Nanoparticles Induce p-Tau Aggregate Formation in Rat Brain?

Abstract

Silver nanoparticles (AgNPs) are incorporated in products such as toys, cosmetics, and surgical tools due to their antimicrobial properties. When animals are exposed, AgNPs bioaccumulate within the brain and persist for months with no clearance. Because of their remarkable physical properties, AgNPs pass through the blood-brain barrier. Once inside, AgNPs disrupt crucial structural proteins such as f-actin. Tau, a critical scaffolding protein, maintains cytoskeletal structure. Through mechanisms such as oxidative stress (OS), tau becomes hyperphosphorylated and forms aggregates, causing cells to lose signaling capabilities and undergo apoptosis. Because it has been demonstrated that AgNPs increase OS and we showed that AgNPs bioaccumulate and persist with no clearance and disrupt the dynamic organization of cytoskeletal proteins, the aim of this project was to determine if AgNPs induce p-tau aggregates. Through immunohistochemistry, we found the accumulation of p-tau aggregates. Preliminary data show that AgNPs increase p-tau accumulation after exposure to low doses of AgNPs while there is no change in rats exposed to high doses of AgNPs. Superoxide Dismutase 1 (SOD1), an enzyme responsible for breaking down toxic reactive oxygen species, expression appears to increase in rats exposed to both low and high doses of AgNPs. These findings suggest that exposure to AgNPs could induce cellular mechanisms associated with neurogenerative diseases and activate SOD1-mediated repair mechanisms. This material is supported under NSF Cooperative Agreement #OIA-2242771 and MUCDRS to R.S.