Microglial activation and pyroptosis induced by nano-TiO2 in marine medaka brain

Recently, nano-titanium dioxide (nano-TiO₂) has been widely distributed over surface water. However, there are few reports on its effects on the central nervous system of fish. In this study, we investigated whether nano-TiO₂ enters the medaka brain after exposure and its effect on the brain. Marine medaka brains were examined after exposure to 0.01 g/L nano-TiO₂ for 3, 10, and 20 d. Nano-TiO₂-like particles were found in the telencephalon of treated fish. There was no obvious brain histopathological injury. The number of irregular mitochondria with absent cristae increased. Gene expression of the apoptosis-related genes, casp8, bcl2b, and bax, decreased significantly in the nano-TiO₂ group at 3 d. In contrast, the pyroptosis-related genes, gsdmeb and casp1, and inflammation-related factor, il18, increased significantly. As an activated microglia marker, mRNA expression of cd68 increased significantly in the nano-TiO₂ treated group. Moreover, CD68 protein expression also increased significantly at 10 d. Altogether, we show that nano-TiO₂ can alter mitochondrial morphology in the telencephalon of medaka, leading to microglial activation and pyroptosis.