Mechanism of TiO₂ nanoparticle‐induced neurotoxicity in zebrafish (Danio rerio)

Abstract

Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 μg/L TiO2 NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C-jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO2 NPs.

Discovery and ramifications of incidental Magnéli phase generation and release from industrial coal-burning

“…TiO 2 nanoparticle toxicity has been extensively examined in the context of freshwater and marine environments and in organisms belonging to several trophic levels 45–48 . It is generally thought that oxidative stress is the primary mechanism of acute toxicity to developing organisms due to the ability of forms of TiO 2 to produce reactive oxygen species (ROS) when irradiated 49–52 . ROS leads to cell death via protein, lipid, and DNA damage 45, 46, 48 .…”

“…ROS leads to cell death via protein, lipid, and DNA damage 45, 46, 48 . There is also evidence that sub-chronic exposure to adult zebrafish causes neurological effects associated with spatial recognition memory and behavior 52 . Several studies implicate TiO 2 nanoparticle coating, shape, size, and aggregation properties as confounding variables to these nanoparticle’s bioavailability and toxicity 45, 46, 50, 53 .…”

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

“…Sheng et al [81] also evaluated TiO 2 nanoparticle-induced neurotoxicity using zebrafish model. It has been reported that TiO 2 nanoparticle significantly activated expressions of different genes such as BDNF C-fos and C-jun.…”

Developmental exposure to silver nanoparticles at environmentally relevant concentrations alters swimming behavior in zebrafish (Danio rerio)

“…The zebrafish is a vertebrate model that has been used extensively to evaluate NP toxicity (Harper et al 2015;Wehmas et al 2015;Sheng et al 2016;Ginzburg et al 2018;Nix et al 2018). It was recently reported that exposure of embryonic zebrafish to Ag-NPs at concentrations far greater than those observed in the environment caused morphological and physiological abnormalities (Cunningham et al 2013;Gao et al 2015).…”