Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.

• Material Type: 博士論文
• Title: Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.
• Author/Editor: Yokoyama, Shohei; Nakagawa, Ichiro; Ogawa, Yoichi; Morisaki, Yudai; Motoyama, Yasushi; Park, Young Su; Saito, Yasuhiko; Nakase, Hiroyuki
• Author Heading: Yokoyama, Shohei; Nakagawa, Ichiro; Ogawa, Yoichi; Morisaki, Yudai; Motoyama, Yasushi; Park, Young Su; Saito, Yasuhiko; Nakase, Hiroyuki
• Publication, Distribution, etc.: Public Library of Science
• Publication Date: 2019-04-12
• Publication Date (W3CDTF): 2019-04-12
• Alternative Title: マウス海馬神経細胞におけるIschemic postconditioning はミトコンドリア局在KATP チャンネルを介してグルタミン酸放出を抑制し神経保護効果をもたらす。
• Periodical title: PloS one
• No. or year of volume/issue: 14 4
• Volume: 14
• Issue: 4
• Pages: Article No.e0215104-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2020-12-24
• Dissertation Number: 乙第1484号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Target Audience: 一般
• Note (General): type:Thesis; A mild ischemic load applied after a lethal ischemic insult reduces the subsequent ischemia-reperfusion injury, and is called ischemic postconditioning (PostC). We studied the effect of ischemic PostC on synaptic glutamate release using a whole-cell patch-clamp technique. We recorded spontaneous excitatory post-synaptic currents (sEPSCs) from CA1 pyramidal cells in mouse hippocampal slices. The ischemic load was perfusion of artificial cerebrospinal fluid (ACSF) equilibrated with mixed gas (95% N2 and 5% CO2). The ischemic load was applied for 7.5 min, followed by ischemic PostC 30 s later, consisting of three cycles of 15 s of reperfusion and 15 s of re-ischemia. We found that a surging increase in sEPSCs frequency occurred during the immediate-early reperfusion period after the ischemic insult. We found a significant positive correlation between cumulative sEPSCs and the number of dead CA1 neurons (r = 0.70; p = 0.02). Ischemic PostC significantly suppressed this surge of sEPSCs. The mitochondrial KATP (mito-KATP) channel opener, diazoxide, also suppressed the surge of sEPSCs when applied for 15 min immediately after the ischemic load. The mito-KATP channel blocker, 5-hydroxydecanoate (5-HD), significantly attenuated the suppressive effect of both ischemic PostC and diazoxide application on the surge of sEPSCs. These results suggest that the opening of mito-KATP channels is involved in the suppressive effect of ischemic PostC on synaptic glutamate release and protection against neuronal death. We hypothesize that activation of mito-KATP channels prevents mitochondrial malfunction and breaks mutual facilitatory coupling between glutamate release and Ca2+ entry at presynaptic sites.; 博士（医学）・乙第1484号・令和2年12月24日; Copyright: © 2019 Yokoyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; identifier:PloS one Vol.14 No.4 Article No.e0215104 (2019 Apr); identifier:19326203; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3829; identifier:PloS one, 14(4): Article No.e0215104
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1371/journal.pone.0215104
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3829/1/01%e4%b9%991484%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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