Marissa Watanabe,1 Kai Roshto,2 Alexandru Sasuclark,1 Matthew W. Pitts1
1 Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaiʻi, Honolulu, HI
2 University of Hawaiʻi at Mānoa, Honolulu, HI
In this study, we examined the interactive effects of Se and MeHg on PVI and PNN maturation in vitro. Mixed primary cortical cultures were raised in Se optimal media (100 nM Se) until DIV14 (days in vitro), after which they were challenged with a subtoxic dose of MeHg (200 nM) from DIV14-DIV28, a critical period when cortical networks and PNNs stabilize. At DIV28, MeHg treatment impaired antioxidant defense, as activity of thioredoxin and thioredoxin reductase were significantly decreased. Electrophysiological analysis using microelectrode arrays (MEA) further revealed that MeHg treatment disrupted neural network connectivity and impaired synaptic plasticity. Moreover, administration of additional Se (400 nM) from DIV14-DIV28 mitigated many of these effects, demonstrating a protective role against MeHg. Altogether, these results demonstrate the interactive effects of Se and MeHg on redox homeostasis and GABAergic maturation.
