Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice

• Material Type: 博士論文
• Title: Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice
• Author/Editor: 坂井, 淳彦
• Author Heading: 坂井, 淳彦
• Publication Date: 2018-06-30
• Publication Date (W3CDTF): 2018-06-30
• Alternative Title: 胎仔期抗てんかん薬曝露によって誘導される異所性ニューロン新生は成体マウスのけいれん感受性を亢進する
• Degree Grantor: 九州大学
• Date Granted: 2018-06-30
• Date Granted (W3CDTF): 2018-06-30
• Dissertation Number: 甲第14149号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第14149号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 (Cxcr4), consequently increasing the ectopic localization of newborn neurons in the hilus. We also found that voluntary exercise in a running wheel suppressed this ectopic neurogenesis and countered the enhanced seizure susceptibility caused by prenatal VPA exposure, probably by normalizing the VPA-disrupted expression of multiple genes including Cxcr4 in adult NS/PCs. Replenishing Cxcr4 expression alone in NS/PCs was sufficient to overcome the aberrant migration of newborn neurons and increased seizure susceptibility in VPA-exposed mice. Thus, prenatal exposure to an AED, VPA, has a long-term effect on the behavior of NS/PCs in offspring, but this effect can be counteracted by a simple physical activity. Our findings offer a step to developing strategies for managing detrimental effects in offspring exposed to VPA in utero.
• DOI: info:doi/10.1073/pnas.1716479115; https://doi.org/info:doi/10.1073/pnas.1716479115
• Persistent ID (NDL): info:ndljp/pid/11178473; https://dl.ndl.go.jp/pid/11178473
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-11-05T10:48:21+09:00
• Date Created (W3CDTF): 2018-08-07
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/2324/1937178
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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