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Astrocytes protect neurons in the hippocampal CA3 against ischemia by suppressing the intracellular Ca2+ overload
http://hdl.handle.net/10271/00003565
http://hdl.handle.net/10271/000035652d3ba840-c3ee-4b6e-b650-1b95e56d66df
| 名前 / ファイル | ライセンス | アクション |
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論文本文 (4.5 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2019-07-09 | |||||||
| タイトル | ||||||||
| タイトル | Astrocytes protect neurons in the hippocampal CA3 against ischemia by suppressing the intracellular Ca2+ overload | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | astrocyte | |||||||
| キーワード | ||||||||
| 主題 | brain ischemia | |||||||
| キーワード | ||||||||
| 主題 | neuroprotection | |||||||
| キーワード | ||||||||
| 主題 | intracellular Ca2+ overload | |||||||
| キーワード | ||||||||
| 主題 | delayed neuronal death | |||||||
| 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 | アストロサイトは細胞内Ca2+の過負荷を抑制して虚血から海馬CA3ニューロンを保護する | |||||||
| 著者 |
孫, 伝奇
× 孫, 伝奇
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| 書誌情報 |
en : Frontiers in cellular neuroscience 巻 12, 号 280, 発行日 2018-08-24 |
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| 出版者 | ||||||||
| 出版者 | Frontiers Research Foundation | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | In the hippocampus, delayed neuronal death is normally seen in neurons of the CA1 region but not in those of the CA3 region. Astrocytes have been reported to play multiple supporting or pathological roles in neuronal functioning. While evidence indicates that astrocytes could exert neuroprotective effects following ischemia, the possible underlying mechanisms remain unclear. We aimed to investigate the roles of astrocytes in the process of delayed neuronal death following transient forebrain ischemia. L-α-aminoadipic acid (L-α-AAA), an astrocyte-selective gliotoxin, was injected into the hippocampal CA3 region of rats through a cranial window to selectively damage astrocytes. Immunofluorescence staining of glial fibrillary acidic protein (GFAP) was used to evaluate the effect of L-α-AAA on astrocyte numbers. Three days after the L-α-AAA injection, transient forebrain ischemia was induced by a modification of the four-vessel occlusion procedure. Seven days after transient forebrain ischemia, hematoxylin-eosin staining was performed to reveal the morphology of hippocampal pyramidal neurons. In rats with ischemia and reperfusion, regional cerebral blood flow (rCBF) and change in intracellular Ca2+ concentration ([Ca2+]i) were separately measured in CA1 and CA3 regions. L-α-AAA injection significantly decreased the number of astrocytes in CA3, but did not affect the pattern of rCBF changes upon ischemia/reperfusion. Seven days after transient forebrain ischemia, in rats receiving L-α-AAA, delayed neuronal death comparable with that in CA1 was observed in the CA3 region. In addition, the pattern of increase in [Ca2+]i due to transient forebrain ischemia was completely changed in the hippocampal CA3. The loss of astrocytes induced a persistent increase in [Ca2+]i in the CA3 region following transient ischemia, similar to what is observed in the CA1 region. Our study indicates that astrocytes in the hippocampal CA3 region exert neuroprotective effects following transient forebrain ischemia and act by suppressing the intracellular Ca2+ overload. Furthermore, our study will most likely provide a new therapeutic strategy for brain ischemic diseases, targeted to astrocytes. | |||||||
| 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 | 2018-09-21 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第788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 | 30197589 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.3389/fncel.2018.00280 | |||||||
| 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 | |||||||
