Abstract
Developmental neurotoxicity (DNT) caused by environmental chemicals is a great concern because the number of patients with neurodevelopmental disorders has been increasing in recent years. Although the DNT guideline test have been updated in 2007, it still has some disadvantages of high-cost and low time efficiency. Thus, to perform in vivo DNT tests efficiently, a new technology is required that can more easily detect chemical-induced DNT. Here, we created a transgenic (Tg) mouse expressing the reporter gene (luciferase; Luc) under the control of a promoter of neuronal differentiation marker and evaluated its usefulness in detecting DNT. Luc activity peaked immediately after birth, decreased with age, and reached plateaus after the weaning period. These changes in Luc expression are thought to reflect the state of brain neural differentiation. Next, we evaluated the temporal changes of in vivo luminescence in the developing brain of Tg mice treated with sodium valproate (VPA) under the conditions that induce autistic spectrum disorder-like symptoms. In vivo luminescence in the brain of VPA-treated group significantly decreased from postnatal day 4 to weaning. Furthermore, both the number of neurons and Luc activity decreased in the prefrontal cortex of VPA-treated group at 8 weeks postpartum. These results suggest that Luc expression may be a marker reflecting the state of brain neural differentiation. In vivo luminescence using our Tg mice could be a potential tool for detecting chemical-induced DNT on developing brain easily.
