Spinal nerve defects induced by prenatal valproic acid exposure

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461634
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: FUKUI Yoshihiro 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (50144168)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 抗てんかん薬 / バルプロ酸 / 脊髄神経 / 発達障害 / 神経管閉鎖不全 / 葉酸

Outline of Final Research Achievements

We examined effects of prenatal exposure to valproic acid (VPA) on the development of the nervous system. VPA (100-400 mg/kg) was subcutaneously injected to pregnant ICR mice on gestational day (GD) 6, 7, 8, or 9. And their embryos were collected on GD 10. The whole-mount immunostaining using an anti-neurofilament antibody clearly identified nerve fiber bundles and dorsal ganglia consisting of spinal nerves. The incidence of these spinal nerve defects (SNDs) was significantly increased in the embryos exposed to VPA on GD 8. The incidence of SNDs caused by VPA administration was increased in a dose dependent manner Folic acid supplementation (3 mg/kg/day) during GD 6-10 reduced the incidence of VPA-induced neural tube defects (NTDs), but not SNDs. Thus, NTDs and SNDs after prenatal VPA-exposure might be induced by different mechanisms.

Free Research Field

先天異常学