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Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
http://hdl.handle.net/10271/2795
http://hdl.handle.net/10271/2795320c1c25-b161-43ba-9f2b-8aba01a7ced9
名前 / ファイル | ライセンス | アクション |
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論文本文 (879.5 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2015-03-06 | |||||
タイトル | ||||||
タイトル | Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | taurine | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | GABAA receptor | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | tonic current | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | radial migration | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | non-vesicular release | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | volume-sensitive anion channel | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | GAD67 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | taurine transporter | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
その他のタイトル | ||||||
その他のタイトル | 胎生期マウス大脳皮質神経細胞の放射状移動におけるタウリン誘発性持続的GABAA受容体活性化の役割 | |||||
言語 | ja | |||||
著者 |
Furukawa, Tomonori
× Furukawa, Tomonori |
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書誌情報 |
en : Frontiers in cellular neuroscience 巻 8, p. 88, 発行日 2014-03 |
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出版者 | ||||||
出版者 | Frontiers | |||||
言語 | en | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | Copyright 2014 Furukawa, Yamada, Akita, Matsushima, Yanagawa and Fukuda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | γ-Aminobutyricacid(GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose?response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAR blockade in GAD67GFP/GFPA mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex. | |||||
言語 | en | |||||
学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医学) | |||||
学位の区分 | ||||||
内容記述タイプ | Other | |||||
内容記述 | doctoral | |||||
言語 | en | |||||
学位の分野 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 医学系研究科 | |||||
言語 | ja | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13802 | |||||
言語 | ja | |||||
学位授与機関名 | 浜松医科大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2014-06-20 | |||||
学位授与番号 | ||||||
学位授与番号 | 乙第513号 | |||||
EISSN | ||||||
収録物識別子タイプ | EISSN | |||||
収録物識別子 | 1662-5102 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 24734001 | |||||
出版社DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.3389/fncel.2014.00088 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |