徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.医学部.医学科.発生発達医学講座.機能解剖学分野

1. (英) Juramt Bold / (日) Juramt Bold / (読) じゅらむと ぼるど

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2. 坂田 ひろみ

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3. 福井 義浩

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(英) Spinal nerve defects in mouse embryos prenatally exposed to valproic acid

(英) To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures.

1. (英) Article.PublicationTypeList.PublicationType: Journal Article

2. (英) KeywordList.Keyword: Developmental neurotoxicity

3. (英) KeywordList.Keyword: Folic acid

4. (英) KeywordList.Keyword: Mice

5. (英) KeywordList.Keyword: Spinal nerve

6. (英) KeywordList.Keyword: Valproic acid