Molecular mechanism of nanoparticulate <scp>TiO<sub>2</sub></scp> induction of axonal development inhibition in rat primary cultured hippocampal neurons
Xu Mu, Wuyan Li, Xiao Ze, Lingjuan Li, Guoqing Wang, Fashui Hong, Yuguan Ze
Abstract
Abstract Numerous studies have demonstrated the in vitro and in vivo neurotoxicity of nanoparticulate titanium dioxide (nano‐TiO 2 ), a mass‐produced material for a large number of commercial and industrial applications. The mechanism of nano‐TiO 2 ‐induced inhibition of axonal development, however, is still unclear. In our study, primary cultured hippocampal neurons of 24‐hour‐old fetal Sprague‐Dawley rats were exposed to 5, 15, or 30 μg/mL nano‐TiO 2 for 6, 12, and 24 hours, and the toxic effects of nano‐TiO 2 exposure on the axons development were detected and its molecular mechanism investigated. Nano‐TiO 2 accumulated in hippocampal neurons and inhibited the development of axons as nano‐TiO 2 concentrations increased. Increasing time in culture resulted in decreasing axon length by 32.5%, 36.6%, and 53.8% at 6 hours, by 49.4%, 53.8%, and 69.5% at 12 hours, and by 44.5%, 58.2%, and 63.6% at 24 hours, for 5, 15, and 30 μg/mL nano‐TiO 2 , respectively. Furthermore, nano‐TiO 2 downregulated expression of Netrin‐1, growth‐associated protein‐43, and Neuropilin‐1, and promoted an increase of semaphorin type 3A and Nogo‐A. These studies suggest that nano‐TiO 2 inhibited axonal development in rat primary cultured hippocampal neurons and this phenomenon is related to changes in the expression of axon growth‐related factors.