Retardation of Axonal and Dendritic Outgrowth Is Associated with the MAPK Signaling Pathway in Offspring Mice Following Maternal Exposure to Nanosized Titanium Dioxide

Exposure to nano titanium oxide (TiO2) has been proven to suppress brain growth in mouse offspring; however, whether retardation of axonal or dendritic outgrowth is associated with activation of the mitogen-activated protein kinase (MAPK) pathway remains unclear. In the present study, pregnant mice were exposed to nano-TiO2 at 1.25, 2.5 and 5 mg/kg body weight, respectively, and the molecular mechanism of axonal or dendritic outgrowth retardation was investigated. The results suggested that nano-TiO2 crossed the blood-fetal barrier and blood-brain barrier and deposited in the brain of offspring, which retarded axonal and dendritic outgrowth, including the absence of axonal outgrowth, and decreased dendritic filament length, dendritic branching number and dendritic spine density. Importantly, maternal exposure to nano-TiO2 increased phosphorylated (p)-extracellular signal-regulated kinase1/2 (ERK1/2, +24.35% to +59.4%), p-p38 (+60.82% to 181.85%) and p-c-jun N-terminal kinase (JNK, +28.28% to 97.28%) expre...