多能性幹細胞の神経系分化誘導と金属による神経毒性研究への応用

DOI Web Site Web Site PubMed 参考文献8件 オープンアクセス

書誌事項

タイトル別名
  • Neural Differentiation of Pluripotent Stem Cells and Application for Metal-induced Neural Toxicity Study
  • Symposium Review : 多能性幹細胞の神経系分化誘導と金属による神経毒性研究への応用
  • Symposium Review : タノウセイ カンサイボウ ノ シンケイケイ ブンカ ユウドウ ト キンゾク ニ ヨル シンケイ ドクセイ ケンキュウ エ ノ オウヨウ

この論文をさがす

抄録

  Metals are effectively used in biological systems under the strict regulation for exploiting their specific and broad reactivities. For example, manganese (Mn) can induce catecholamines-mediated oxidative biological damage in cooperation with iron (Fe) and/or copper (Cu). In children, the damage could induce developmental disorders such as attention deficit hyperactivity disorder (ADHD). We hypothesize that infant neurons are more labile to metals than adult ones due to the prematured protection systems and sensitive differentiating cells. An experimental system reconstituting neural differentiation is expected to assess the influences of endogenous/exogenous factors including metals. In this study, we investigated an impact of Mn together with Fe and dopamine (DA) on neural differentiation of mouse embryonic stem cells (mESCs). The differentiation of mESCs was initiated by embryoid bodies (EBs) formation in the presence of all-trans retinoic acid, and then EBs were treated with Mn, Fe and/or DA. Then, the mRNA levels of neural differentiation marker genes (Nestin, Emx2, Mtap2, Th, Olig2 and Gfap) were examined using realtime RT-PCR analysis. Mn or DA alone reduced Mtap2, Th and Olig2 expression levels and increased Nestin. Moreover, combined treatment of Mn and DA also increased Nestin expression level. On the other hand, Fe alone reduced Mtap2, Th and Olig2 expression levels, and increased Emx2. Combined treatments of Fe with Mn or DA also tended to increase Emx2 expression level. These effects emerged at about 100 times less concentration than that inducing cytotoxicity in human neuroblastoma. The present study showed that Mn inhibits neural development, and that our mESCs system can be a useful tool to elucidate the toxicity mechanism as well as to evaluate the effects of metals and chemicals on differentiating cells.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 134 (7), 793-795, 2014-07-01

    公益社団法人 日本薬学会

参考文献 (8)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ