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- Title
Multimodal Imaging for DREADD-Expressing Neurons in Living Brain and Their Application to Implantation of iPSC-Derived Neural Progenitors.
- Authors
Hiroyuki Kaneko; Takafumi Minamimoto; Chie Seki; Maiko Ono; Masaki Tokunaga; Ryong-Moon Shin; Takeharu Minamihisamatsu; Ji, Bin; Tetsuya Suhara; Makoto Higuchi; Hiroki Takeuchi; Koji Tanabe; Haruhisa Inoue; Katsushi Kumata; Ming-Rong Zhang; Ichio Aoki; Tsukamoto, Satoshi; Seiji Kito; Richmond, Barry J.
- Abstract
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.
- Subjects
NEURAL physiology; DESIGNER drugs; CLOZAPINE; INDUCED pluripotent stem cells; POSITRON emission tomography
- Publication
Journal of Neuroscience, 2016, Vol 36, Issue 45, p11544
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1279-16.2016