CAREER: Physiological responses of neural stem cells to low-level silver nanoparticles.

Proposal: 1553667 -<br/><br/>PI: Spitzer, Nadia Ph.D.<br/><br/>Consumers today are in contact with hundreds of products that boast antimicrobial properties because they contain manufactured silver nanoparticles. These products include wound dressings, food containers, toys, toothbrushes, clothing, cosmetics, and household appliances. The silver nanoparticles may be shed from these products resulting in exposure. The antibacterial properties of silver have been recognized since before modern medicine; however, the specific shape and size of silver nanoparticles make them act differently than larger forms of silver. Specifically, they may cross barriers that other forms of silver cannot, following repeated exposures. This project examines the responses of brain cells to low-levels of silver nanoparticles such as those that might result from daily exposure. The PI use a special type of brain cell, adult neural cells. The results of this research will improve our understanding of the impact of widespread incorporation of silver nanoparticles in consumer products. It will also contribute to regulatory policies.<br/><br/>The proposed work will investigate the cellular and molecular effects of chronic low-level exposures to silver nanoparticles (AgNPs) on neural physiology and development. It utilizes adult neural cells as a model to test the effects of low levels of AgNPs on neural cell physiology in identified cells in vitro and in vivo. In vitro studies
will identify the intracellular signaling pathways targeted by AgNP exposure to mediate deficits
in cytoskeletal structure and function. This will be assessed by combining pharmacology with immunocytochemistry, immunoblot, and time-lapse microscopy of differentiating adult neural cells in culture. The passive and active membrane properties of living cells exposed to low-level AgNPs will be measured by patch clamp electrophysiology to quantify effects on cell physiology during differentiation. Building on in vitro findings, neurogenesis in the brain after chronic, sub-lethal oral AgNP exposure will be investigated using rats. This work represents a critical step towards understanding the cellular targets of sub-lethal AgNPs on neural cells with respect to the physiological mechanisms operating in individual cells. The proposed work includes a significant public education effort that involves undergraduate students in bringing science to elementary schools throughout rural West Virginia. Children will learn scientific concepts in fun interactive ways and meet accessible role models for choosing careers in science or technology.