Effects of oral silver nanoparticle exposure on synapse morphology in the rat brain.

Abstract

Silver nanoparticles (AgNPs) possess antimicrobial properties and are incorporated into various medical and consumer products. These particles are released from products during use and bioaccumulate in the brain. Previously, we found that AgNPs disrupt cytoskeletal mechanisms in cultured neural cells. Because synapse morphology is highly dependent on the actin cytoskeleton, we hypothesized that synapse structure is disrupted through oral AgNP exposure in rats. We treated rats orally with AgNP solutions in 10% sucrose with either 0 mg/kg (control), 25 mg/kg (low), or 100 mg/kg of AgNPs (high). These amounts were chosen because the AgNP concentrations accumulated in the rat brain after treatment with these doses mirror the concentrations estimated to accumulate in the human brain from environmental exposure. Brains were collected after nine weekdays of consecutive treatment or following a month of no AgNP treatment to examine if the bioaccumulation of AgNPs impacts synapse morphology. Immunohistochemistry (IHC) was used to identify changes in presynaptic terminal markers and postsynaptic terminal markers. When the terminals maintain the apposition necessary for function, the green presynaptic signal and the red postsynaptic signal colocalize yellow when imaged using confocal microscopy. The colocalizations were quantified using the SynBot plugin for Fiji. Our data suggest that oral AgNP exposure decreases pre- and post-synaptic colocalization in the hippocampus. Because synapses in the hippocampus are essential for learning and memory, these processes could be disrupted by AgNP bioaccumulation. This material is supported by MUCD award to AB, NASA WVSC scholarship to RS, and NSF Cooperative Agreement #OAI-2242771.