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Please use this identifier to cite or link to this item: http://hdl.handle.net/10271/3208

Title: A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence
Other Titles: 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
Authors: Kakizawa, Keisuke
柿沢, 圭亮
Issue Date: 17-Aug-2016
Publisher: American Association for the Advancement of Science
Abstract: 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.
Description: 浜松医科大学学位論文 医博第739号(平成28年11月18日)
URI: http://hdl.handle.net/10271/3208
DOI: info:doi/10.1126/sciadv.1501723
PubMed ID: info:pmid/27540587
Academic Degrees and number: 13802甲第739号
Degree-granting date: 2016-11-18
Degree name: 博士(医学)
Degree-granting institutions: 浜松医科大学
Appears in Collections:2010 博士(論文)

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