Akt and MAPK/ERK signaling regulate neurite extension in adult neural progenitor cells but do not directly mediate disruption of cytoskeletal structure and neurite dynamics by low-level silver nanoparticles

Silver nanoparticles (AgNPs) are an environmental contaminant of emerging concern. Ionic and colloidal silver has long been used for its antimicrobial properties, but with the development of engineered AgNPs, these are increasingly incorporated in the manufacture of nano-enhanced products. AgNPs are released into the environment from manufacturing plants and they can be shed from products during use and after disposal. This can lead to chronic low-level environmental exposure in animals. Unlike traditional forms of silver, the unique physical properties of AgNPs allow them to bypass biological barriers and enter tissues, like the brain, where they can bioaccumulate. Thus, it is important to understand if low-level AgNPs induce physiological changes in brain cells. Previously we found that 1.0 ?g/mL AgNP exposure resulted in disruption of f-actin organization and neurite collapse in cultured differentiating adult neural stem cells, and that interaction with ?-catenin signaling was involved. Here, we report that AgNP exposure may interact with pAkt signaling irreversibly or indirectly to disrupt cytoskeleton and inhibit neurite extension. Furthermore, the MAPK/ERK signaling pathway is not a target for AgNP-mediated dysregulation. Environmental exposure to low-level AgNPs therefore appears to target specific cellular mechanisms to alter brain cell physiology. Understanding these underlying mechanisms is important for decisions regulating the use and disposal of manufactured AgNPs.

Automated summary

Environmental exposure to low-level AgNPs may lead to physiological changes in brain cells through mechanisms involving disruption of f-actin organization, neurite collapse, and interaction with pAkt signaling. Understanding these mechanisms is important for regulating the use and disposal of AgNPs.