Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Improving the safety of nanomaterials (NMs), which are key materials in nanotechnology, is an important concern in the development of this field. To achieve safer NMs by design, it is essential to understand the underlying causes of their unique biological effects, particularly those that differentiate them from other chemicals. Hence, we have sought to identify the specific toxicities of NMs and to elucidate their mechanisms. In particular, we have focused on the developmental neurotoxicity of NMs, a concern raised at the international conference. Titanium dioxide nanoparticles (TiO2-NPs) or carbon black nanoparticles (CB-NPs), which are widely used as NMs, were intratracheally administered (3-95 µg/kg) to ICR mice on gestational days 5 and 9, and brains were collected from 6- and 12-week-old pups. Histopathological changes of the entire brain tissues were investigated, and the detected abnormal areas were evaluated using in situ infrared spectroscopy and protein expression analysis. Maternal exposure to NMs resulted in enlarged granules of perivascular macrophages responsible for removal of waste proteins. In astrocytes adjacent to the abnormal perivascular macrophages, GFAP and AQP4 were observed to dose-dependently increase, indicating that maternal exposure to NMs induces astrogliosis around the blood vessels. Furthermore, comparison of infrared spectra revealed a spectral shift indicating protein denaturation only around the denatured blood vessels. Both these astrocytes and perivascular macrophages showed an increase in endoplasmic reticulum stress markers (ATF6 and CHOP), along with accumulation of abnormal structural proteins. These findings suggest that maternal exposure to NMs can cause brain perivascular abnormalities, which may be due to the accumulation of denatured structural proteins.
