【博士論文】学術データベース

博士論文 / A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence 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

書誌事項

タイトル

A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence

タイトル別名

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

著者名

Kakizawa Keisuke

著者名

柿沢圭亮

学位授与大学

浜松医科大学 (大学ID:0079) (CAT機関ID:KI000480)

取得学位

博士(医学)

学位授与番号

甲第739号

学位授与年月日

2016-08-17

注記・抄録

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.

浜松医科大学学位論文 医博第739号(平成28年11月18日)

PubMed番号 : info:pmid/27540587

各種コード

NII論文ID(NAID)

500001044330

NII著者ID(NRID)
  • 8000001156360
  • 8000001156361
DOI (出版社)

10.1126/sciadv.1501723

DOI

info:doi/10.1126/sciadv.1501723

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

外部リンク

DOI

博士論文 / 浜松医科大学 / 医学

博士論文 / 浜松医科大学

博士論文 / 医学

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