Abstract
Recently, human epidemiological studies have revealed that maternal immune activation (MIA) during pregnancy increases the risk of neurodevelopmental disorders. There is growing concern that MIA may also contribute to developmental neurotoxicity (DNT) induced by chemical exposure. However, the specific chemicals that trigger MIA and the detailed mechanism of MIA-induced DNT remain unknown. Current guideline tests for DNT are time-consuming, labor-intensive, and require a significant number of laboratory animals. Therefore, there is a need to develop a simple and objective evaluation method that can be applied during the early postnatal period. Against this backdrop, we had previously generated the neuronal differentiation tracer mice (Syn-Rep mice), which express luciferase (Luc) under the control of neuronal differentiation marker promoter and have shown that the effects of chemicals that may induce neuronal cell death can be evaluated noninvasively by in vivo imaging. Here, we examined the usefulness of Syn-Rep mice as a tool to evaluate DNT caused by MIA using the Poly(I:C)-based MIA model. In vivo imaging revealed that Luc activity in the brains of Poly(I:C)-treated offspring was altered compared to the control group. Additionally, the number of microglia and astrocytes in the hippocampus of Poly(I:C)-treated animals was increased compared to the control group. These results suggest that Syn-Rep mice may be able to noninvasively detect MIA-induced DNT by assessing brain Luc activity. Syn-Rep mice are expected to be a useful tool in future studies of MIA-induced DNT.
