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サルの脳回路を特異的に操作する化学遺伝学とイメージングの融合手法

https://repo.qst.go.jp/records/67004
https://repo.qst.go.jp/records/67004
7a4d7732-7db4-494f-a593-3b99ef526365
Item type 会議発表用資料 / Presentation(1)
公開日 2018-11-26
タイトル
タイトル サルの脳回路を特異的に操作する化学遺伝学とイメージングの融合手法
言語
言語 jpn
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 南本, 敬史

× 南本, 敬史

WEKO 658677

南本, 敬史

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南本 敬史

× 南本 敬史

WEKO 658678

en 南本 敬史

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内容記述タイプ Abstract
内容記述 We developed a new ligand, a carbon-11-labeled derivative of DREADD agonists (Chen et al., 2015), to improve the sensitivity of DREADD-PET imaging. In vitro assay demonstrated that, unlike clozapine, the derivative did not display high potency for major endogenous G protein coupled receptors. We examined the new PET ligand in a monkey that received injections of an hM4Di-expressing viral vector into the unilateral putamen. As seen with 11C-clozapine, PET imaging localized an increased uptake of the new ligand at the putative hM4Di-expressing site. Compared with 11C-clozapine, the signal-to-noise ratio was largely improved; the ligand uptake at the putative hM4Di-expressing site was enhanced by about 10%, while the baseline uptakes in the striatum or other subcortical areas were reduced by about 30%. Pretreatment with an unlabeled ligand at a dose of 1 mg/kg almost completely diminished the uptake at the injection site, and therefore the ligand uptake appeared to reflect in vivo DREADD expression. Besides the injection site in the putamen, an increased uptake was also found in its projection areas, i.e., the globus pallidus and the substantia nigra, presumably reflecting hM4Di expression at the axon terminal. Two additional monkeys were scanned following bilateral injections of an AAV-hM4Di vector into the rostromedial caudate or the thalamus. In vivo hM4Di expressions in these two subcortical areas were also detected as high ligand uptakes. These results indicate that our new PET ligand provides a high DREADD selectivity in subcortical regions in monkeys, thus being beneficial for quantitative assessment and sensitive detection of DREADD expression even at the axon terminal.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 第三回脳情報の解読と制御研究会
発表年月日
日付 2018-11-24
日付タイプ Issued
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