Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
J Biochem. 2022 Oct 19;172(5):321-327. doi: 10.1093/jb/mvac070.
Brain-derived neurotrophic factor (BDNF) plays a crucial role in numerous brain functions, including memory consolidation. Previously, we generated a Bdnf-Luciferase transgenic (Bdnf-Luc) mouse strain to visualize changes in Bdnf expression using in vivo bioluminescence imaging. We successfully visualized activity-dependent Bdnf induction in living mouse brains using a d-luciferin analog, TokeOni, which distributes to the brain and produces near-infrared bioluminescence. In this study, we compared the patterns of bioluminescence signals within the whole body of the Bdnf-Luc mice produced by d-luciferin, TokeOni and seMpai, another d-luciferin analog that produces a near-infrared light. As recently reported, hepatic background signals were observed in wild-type mice when using TokeOni. Bioluminescence signals were strongly observed from the region containing the liver when using d-luciferin and TokeOni. Additionally, we detected signals from the brain when using TokeOni. Compared with d-luciferin and TokeOni, signals were widely detected in the whole body of Bdnf-Luc mice by seMpai. The signals produced by seMpai were strong in the regions containing skeletal muscles in particular. Taken together, the patterns of bioluminescence signals in Bdnf-Luc mice vary when using different luciferase substrates. Therefore, the expression of Bdnf in tissues and organs of interest could be visualized by selecting an appropriate substrate.
脑源性神经营养因子（BDNF）在许多大脑功能中起着至关重要的作用，包括记忆巩固。此前，我们生成了一种 Bdnf-Luciferase 转基因（Bdnf-Luc）小鼠品系，使用活体生物发光成像来可视化 Bdnf 表达的变化。我们成功地使用 d-荧光素类似物 TokeOni 可视化了活体小鼠大脑中活性依赖性 Bdnf 诱导，该类似物分布到大脑并产生近红外生物发光。在这项研究中，我们比较了 Bdnf-Luc 小鼠全身的生物发光信号模式，这些信号是由 d-荧光素、TokeOni 和另一种产生近红外光的 d-荧光素类似物 seMpai 产生的。如最近报道的，当使用 TokeOni 时，野生型小鼠中观察到肝背景信号。当使用 d-荧光素和 TokeOni 时，从包含肝脏的区域强烈观察到生物发光信号。此外，当使用 TokeOni 时，我们还检测到来自大脑的信号。与 d-荧光素和 TokeOni 相比，seMpai 在 Bdnf-Luc 小鼠全身更广泛地检测到信号。特别是在包含骨骼肌的区域，seMpai 产生的信号很强。总之，不同荧光素酶底物在 Bdnf-Luc 小鼠中生物发光信号的模式有所不同。因此，通过选择合适的底物，可以可视化感兴趣的组织和器官中 Bdnf 的表达。
