Silver nanoparticle-induced disruption of the tripartite synapse in rat brain.

The antibacterial properties of silver nanoparticles (AgNPs) have led to their incorporation in consumer products such as wound dressings and cosmetics. AgNPs can be released into the environment during product use and manufacturing, leading to possible exposure of animals. AgNPs cross the blood-brain barrier (BBB) and bioaccumulate in brain tissue. AgNP exposure induces disruption of the F-actin cytoskeleton and neurite collapse in cultured neural cells. Disruptions in cytoskeletal integrity can lead to imbalanced synaptic plasticity, as structure is critical for proper synaptic function. Astrocytes play a crucial role in modulating tripartite synaptic signaling with their peripheral astrocytic processes (PAPs). These functions rely on the actin cytoskeleton, as it is critical for structural changes in PAPs and for facilitating bidirectional communication.AgNPs cross the BBB and disrupt F-actin cytoskeleton components, but their impact on astrocytic morphology remains unknown. Given the role of astrocytes in maintaining synaptic morphology, we tested the hypothesis that the bioaccumulation of AgNPs leads to a disruption in tripartite synapse microarchitecture. Using immunohistochemistry for presynaptic and PAP structures, we found a significant decrease in the percentage of presynaptic and PAP colocalizations in the hippocampus and striatum of the rats exposed to AgNPs compared to control. These data suggest that AgNP exposure could disrupt tripartite synapse microarchitecture and lead to improper synaptic functioning, which has been implicated in neurodegeneration. This work could be used to guide the regulation of AgNP usage and disposal during the manufacturing process. This material is supported under NSF Cooperative Agreement #OIA-2242771.