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アイテム
Synaptic modulation mediated by the endocannabinoid 2-arachidonoylglycerol in the central nervous system
https://doi.org/10.15083/00005460
https://doi.org/10.15083/000054609bc7004b-6297-4492-8a75-9267154848a8
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
H24_4013_tanimura.pdf (51.9 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2014-01-14 | |||||
| タイトル | ||||||
| タイトル | Synaptic modulation mediated by the endocannabinoid 2-arachidonoylglycerol in the central nervous system | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| ID登録 | ||||||
| ID登録 | 10.15083/00005460 | |||||
| ID登録タイプ | JaLC | |||||
| その他のタイトル | ||||||
| その他のタイトル | 中枢神経系における内因性カンナビノイド2−アラキドノイルグリセロールによるシナプス修飾 | |||||
| 著者 |
谷村, あさみ
× 谷村, あさみ |
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| 著者所属 | ||||||
| 著者所属 | 東京大学医学系研究科機能生物学専攻 | |||||
| Abstract | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, I analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). Endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. These results clearly indicate that 2-AG produced by DGLα, not by DGLβ, mediates retrograde synaptic suppression. To elucidate how 2-AG signaling is terminated after inducing retrograde synaptic suppression, I examined the cerebellum of mice lacking the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL) or mice with cerebellar granule cell (GC)-specific deletion of MGL. In wild-type cerebellum, MGL was expressed richly in terminals of parallel fibers (PFs), the axons of GCs, and weakly in Bergman glia (BG), but was absent in climbing fiber (CF) terminals and GABAergic terminals. Despite this highly selective MGL expression pattern, 2-AG-mediated retrograde suppression was significantly prolonged at not only PF-Purkinje cell (PC) synapses but also CF-PC synapses in GC-specific MGL knockout mice. Virus-mediated expression of MGL into BG of global MGL-KO mice significantly shortened 2-AG-mediated retrograde suppression at PF-PC synapses. Furthermore, contribution of MGL to termination of 2-AG signaling depended on the distance from MGL-rich PFs to inhibitory synaptic terminals. These results indicate that 2-AG is degraded in a synapse type-independent manner by MGL present in PFs and BG. | |||||
| 書誌情報 | 発行日 2013-03-25 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位 | ||||||
| 値 | doctoral | |||||
| 学位分野 | ||||||
| Medical Science(医学) | ||||||
| 学位授与機関 | ||||||
| 学位授与機関名 | University of Tokyo (東京大学) | |||||
| 研究科・専攻 | ||||||
| Department of Functional Biology, Graduate School of Medicine(医学系研究科機能生物学専攻) | ||||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2013-03-25 | |||||
