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A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence
http://hdl.handle.net/10271/3208
http://hdl.handle.net/10271/3208e95109af-33d3-4ad5-a2af-7a664f18c301
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (7.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2017-11-11 | |||||||
| タイトル | ||||||||
| タイトル | A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 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 | 正中隆起におけるGABAを介した副腎皮質刺激ホルモン放出ホルモン分泌の新たなメカニズム | |||||||
| 著者 |
Kakizawa, Keisuke
× Kakizawa, Keisuke
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| 書誌情報 |
en : Science Advances 巻 2, 号 8, p. e1501723, 発行日 2016-08-17 |
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| 出版者 | ||||||||
| 出版者 | American Association for the Advancement of Science | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Corticotropin-releasing hormone (CRH), which is synthesized in the paraventricular nucleus (PVN) of the hypothalamus, plays an important role in the endocrine stress response. The excitability of CRH neurons is regulated by γ-aminobutyric acid (GABA)-containing neurons projecting to the PVN. We investigated the role of GABA in the regulation of CRH release. The release of CRH was impaired, accumulating in the cell bodies of CRH neurons in heterozygous GAD67-GFP (green fluorescent protein) knock-in mice (GAD67⁺/GFP), which exhibited decreased GABA content. The GABAA receptor (GABAAR) and the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC1), but not the K⁺-Cl⁻ cotransporter (KCC2), were expressed in the terminals of the CRH neurons at the median eminence (ME). In contrast, CRH neuronal somata were enriched with KCC2 but not with NKCC1. Thus, intracellular Cl⁻ concentrations ([Cl⁻]i) may be increased at the terminals of CRH neurons compared with concentrations in the cell body. Moreover, GABAergic terminals projecting from the arcuate nucleus were present in close proximity to CRH-positive nerve terminals. Furthermore, a GABAAR agonist increased the intracellular calcium (Ca²⁺) levels in the CRH neuron terminals but decreased the Ca²⁺ levels in their somata. In addition, the increases in Ca²⁺ concentrations were prevented by an NKCC1 inhibitor. We propose a novel mechanism by which the excitatory action of GABA maintains a steady-state CRH release from axon terminals in the ME. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 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 | |||||||
| 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 | 2016-11-18 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第739号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 2375-2548 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 27540587 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1126/sciadv.1501723 | |||||||
| 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 | |||||||
