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Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys
https://repo.qst.go.jp/records/79673
https://repo.qst.go.jp/records/79673771f2d77-4e5c-471b-a7c6-5ef2b8f70d5b
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-03-26 | |||||
| タイトル | ||||||
| タイトル | Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Nagai, Yuji
× Nagai, Yuji× Miyakawa, Naohisa× Takuwa, Hiroyuki× Hori, Yukiko× Oyama, Kei× Ji, Bin× Manami, Takahashi× Xi-Ping, Huang× T. Slocum, Samuel× F. DiBerto, Jeffrey× Xiong, Yan× Urushihata, Takuya× Hirabayashi, Toshiyuki× Fujimoto, Atsushi× Mimura, Koki× G. English, Justin× Liu, Jing× Ken-ichi, Inoue× Kumata, Katsushi× Seki, Chie× Ono, Maiko× Shimojo, Masafumi× Ming-Rong, Zhang× Tomita, Yutaka× Nakahara , Jin× Suhara, Tetsuya× Takada, Masahiko× Higuchi, Makoto× Jin, Jian× L. Roth, Bryan× Minamimoto, Takafumi× Nagai, Yuji× Miyakawa, Naohisa× Takuwa, Hiroyuki× Hori, Yukiko× Oyama, Kei× Ji, Bin× Manami, Takahashi× Urushihata, Takuya× Hirabayashi, Toshiyuki× Fujimoto, Atsushi× Mimura, Koki× Kumata, Katsushi× Seki, Chie× Ono, Maiko× Shimojo, Masafumi× Ming-Rong, Zhang× Tomita, Yutaka× Suhara, Tetsuya× Higuchi, Makoto× Minamimoto, Takafumi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The chemogenetic technology Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) affords remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities, and potential off-target effects of CNO represent areas for improvement. Here we provide a new high affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg/kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg/kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents the most potent, selective, metabolically stable and fast-acting DREADD agonist reported with utility in both mice and non-human primates for a variety of applications. | |||||
| 書誌情報 |
Nature Neuroscience 巻 23, 号 9, p. 1157-1167, 発行日 2020-07 |
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| 出版者 | ||||||
| 出版者 | Nature Publishing Group | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1097-6256 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 32632286 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41593-020-0661-3 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.nature.com/articles/s41593-020-0661-3 | |||||
