Multimodal imaging for DREADD-expressing neurons in living brain and their application to implantation of iPSC-derived neural progenitors

Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J. Richmond, Tetsuya Suhara, Makoto Higuchi

研究成果: ジャーナルへの寄稿学術論文査読

26 被引用数 (Scopus)

抄録

Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [11C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI). Neural progenitors derived from hM4Di Tg-induced pluripotent stem cells were then implanted into WT mouse brains and neuronal differentiation of the grafts could be imaged by [11C]CNO-PET. Finally, ASL-MRI captured chemogenetic functional manipulation of the graft neurons. Our data provide the first demonstration of multimodal molecular/functional imaging of cells expressing a functional gene reporter in the brain, which would be translatable to humans for therapeutic gene transfers and cell replacements.

本文言語英語
ページ(範囲)11544-11558
ページ数15
ジャーナルJournal of Neuroscience
36
45
DOI
出版ステータス出版済み - 09-11-2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学一般

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