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In vitro screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays
Citation:
Strickland, J., W. Lefew, J. Crooks, D. Hall, J. Ortenzio, K. Dreher, AND Tim Shafer. In vitro screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays. Journal of Nanotoxicology. Taylor and Francis, Philadelphia, PA, 10(5):619-28, (2016).
Impact/Purpose:
The primary impact of this paper to the scientific field is that it presents effects data on 9 different particles on function of neuronal networks; more than has ever been tested previously, and that particles alter both spontaneous as well as pharmacologically-stimulated network activity. These adverse effects occur at very low concentrations for in vitro studies suggesting altered neuro-physiological responses are a sensitive endpoint to assess for adverse health outcomes associated with nanoparticle exposures. Further, effects of particles on different parameters of network function differ and change over time. For the Agency, the paper demonstrates that MEAs can be used to screen particles for their potential to cause neurotoxicity, but that effects cannot be predicted based on particle composition (both TiO2 and CeO2 particles had effects). Although both micro and nano sized particles had effects on network function, there was a clear distinction between micro and nano sized particles in terms of the types of effects. These data provide a means to rank the particles in terms of prioritizing them for additional, in vivo, characterization of health effects.
Description:
Nanoparticles (NPs) may translocate to the brain following inhalation or oral exposures, yet higher throughput methods to screen NPs for potential neurotoxicity are lacking. The present study examined effects of 5 Ce02 (5- 1288 nm), and 4 Ti02 (6-142 nm) NPs and microparticles (MP) on network function in primary cultures of rat cortex on 12 well microelectrode array (MEA) plates. Particles were without cytotoxicity at concentrations ≤ 50 μg/ml. After recording 1h of baseline activity prior to partide (3-50 μg/ml) exposure, changes in the total number ofspikes (TS) and # of active electrodes (#AEs) were assessed 1, 24, and 48 h later. Following the 48 h recording, the response to a challenge with the GABAA antagonist bicuculline (BIC; 25μM) was assessed. In all, particles effects were subtle, but 69 nm Ce02 and 25 nm Ti02 NPs caused concentration-related decreases in TS following 1 h exposure. At 48 h, 5 and 69 nm Ce02 and 25 and 31 nmTi02 decreased #AE, while the two MPs increased #AEs. Following BIC, only 31 nm Ti02 produced concentration-related decreases in #AEs, while 1288 nm Ce02 caused concentration-related increases in both TS and #AE. The results indicate that some metal oxide particles cause subtle concentration-related changes in spontaneous and/or GABAA receptor-mediated neuronal activity in vitro at times when cytotoxicity is absent, and that MEAs can be used to screen and prioritize nanoparticles for neurotoxicity hazard.
