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In vitro screening of silver nanoparticles and ionic silver using neural networks yields differential effects on spontaneous activity and pharmacological responses.
Citation:
Strickland, J., W. LeFew, J. Crooks, D. Hall, J. Ortenzio, K. Dreher, AND Tim Shafer. In vitro screening of silver nanoparticles and ionic silver using neural networks yields differential effects on spontaneous activity and pharmacological responses. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 355(11):1-8, (2016).
Impact/Purpose:
This work evaluates the actions of 6 silver nanoparticles on function of neuronal networks in vitro, and compares those effects to ionic silver. The data demonstrate that 4 of the 6 particles were without effects at concentrations that were not overtly cytotoxic. Effects of 2 particles were subtle. 10 nm silver-citrate coated particles increased the distribution of activity over the network after 24 hrs of exposure, while 75 nm silver-PVP coated particles did so after 48 hrs exposure, but only in response to pharmacological challenge to the network. By contrast, ionic silver decreased these parameters, or was without effect. These results indicate that effects of silver nanoparticles on neural network function, when they occur are small. However, they are qualitatively different from ionic silver.
Description:
Silver nanoparticles (AgNPs) are used in a wide range of consumer and medical products because of their antimicrobial and antifungal properties. Numerous studies have demonstrated that silver can translocate to distal organs following exposure to AgNPs. Therefore, it is essential to examine neural function as part of assessing potential impacts of AgNPs on human health, as exposures to AgNPs are presently a possible risk in both consumer and occupational exposures. The present study examined effects of 3 citrate coated AgNPs, 3 PVP coated AgNPs (10-75 nm) and AgNO3 on spontaneous and pharmacologically-induced neural network function in primary cortical cultures grown on multi-well microelectrode array (mwMEA) plates. For mwMEA experiments, baseline activity (1 h) was recorded prior to exposure to non-cytotoxic concentrations of AgNPs and AgNO3 (0.078-0.63 and 0.08-1.7 μg/ml, respectively). Changes in number of total spikes (TS) and active electrodes (AE), relative to controls, were assessed 1, 24, and 48 h after exposure to Fetal Bovine Serum pre-coated AgNP suspensions or AgNO3. After the 48 h recording, the response to a pharmacological challenge with the GABAA antagonist, bicuculline (BIC; 25 µM), was assessed. Most particles were without effects on neural network function. However, citrate coated 10 nm AgNP caused concentration-related increases in AEs at 24 h. After BIC treatment, PVP coated 75 nm AgNP caused concentration-dependent increases in AE. AgNO3 effects were different from AgNPs, causing a concentration-related decrease in AEs at both 24 and 48 h and a concentration-related decrease in TS following BIC challenge. Importantly, the direction of AgNO3 effects on neuronal activity was opposite those of 10 nm Ag citrate at concentrations up to 0.63 µg/ml, and different from 75 nm Ag PVP, indicating ionic silver does not mediate these effects.
