Abstract
At present, about 10% of pregnant women in Japan have a hypertensive condition, and are diagnosed with pregnancy-induced hypertension. Among the symptoms of pregnancy-induced hypertension, eclampsia is a serious disease that can have serious consequences for both fetuses and pregnant women. A typical symptom is convulsions, and diazepam (DZ) is used as one of the therapeutic drugs. DZ is one of the benzodiazepines and is used as a sedative, anxiolytic, and anticonvulsant. So far, we have shown that DZ and its metabolites, nordazepam (NZ) and oxazepam (OZ), are detected in the fetus when DZ is administered to pregnant mice. In addition, the amount of DZ and its metabolites that distributed to the fetal brain was also analyzed because DZ and its metabolites are easily transferred to the brain. The results showed that when DZ was administered during pregnancy, the metabolite OZ was distributed to fetuses in a larger amount than DZ. That is, it was considered that OZ rather than DZ had a high possibility of affecting the fetal brain. In this study, we analyzed the effects of OZ on the fetal brain in vitro from a developmental viewpoint. The second trimester is a period in which the division of neural stem cells and the differentiation into neurons and astrocytes occur actively in the cerebral cortex region of the fetus, and the effect of OZ on neurogenesis is feared. Therefore, we isolated and cultured neural stem cells from fetal brain of second trimester mice, added OZ, and analyzed effects on differentiation into neurons and astrocytes by immunostaining and RT-PCR. As a result, it was revealed that when OZ was added to neural stem cells, differentiation into astrocytes was suppressed. This study suggests that the use of DZ during the second trimester may affect the finely programmed neural development because OZ suppresses astrocyte differentiation of neural stem cells.
