Development of a medication method to reduce VPA side effects on the fetus

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19783
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Juntendo University
• Principal Investigator: Kinjo Tomoya 順天堂大学, 医学部, 非常勤助教 (80750364)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: バルプロ酸ナトリウム(VPA) / 神経細胞新生 / アセチル化 / BrdU / HDACi / ADHD

Outline of Final Research Achievements

Sodium valproate (VPA) is frequently used for treatment as an antiepileptic drug, but it has been pointed out that medication during pregnancy has an adverse effect on offspring. Therefore, in this study, in order to pursue safe VPA medication and to elucidate its mechanism of action, VPA was administered to pregnant rats and various analyzes were performed on their offspring. As a result of analysis, it has been found that VPA induces attention deficit and spontaneity in offspring and causes behavioral features such as attention deficit / hyperactivity disorder (ADHD). Furthermore, as the mechanism of action, the involvement of neurogenesis and histone tail acetylation was shown. In order to safely take VPA, it is suggested that the dosage is important, and that the side effects of VPA may decrease with the age.

Free Research Field

精神薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、使用頻度が高く、且つ催奇形成のリスクも高いVPA に着目した研究であり、てんかん患者あるいはVPA適応疾患である躁うつ病患者が安心して妊娠・出産するための基礎となる研究である。この研究成果をきっかけにVPA の安全限界が解明されれば、多大な福祉医療費を必要とする自閉症や知的障害のリスクを下げることができる可能性がある。それにより女性の社会進出も可能となり、大きな経済効果も期待できる。