Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared bioluminescence imaging
Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared bioluminescence imaging
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DOI：
10.1186/s13041-020-00665-7
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发表时间：
2020-09-07
期刊：
影响因子：
3.6
通讯作者：
Mori, Hisashi
中科院分区：
文献类型：
--
作者：
Fukuchi, Mamoru;Saito, Ryohei;Mori, Hisashi
脑源性神经营养因子（BDNF）水平的改变已被报道在神经系统疾病的人脑中。因此，重要的是要了解BDNF的表达是如何控制下的病理生理以及生理条件。在这里，我们报告了一种方法来可视化的BDNF表达的变化，在活的小鼠大脑中使用生物发光成像（BLI）。我们以前产生了一种新的转基因小鼠品系，Bdnf-荧光素酶（Luc），以监测Bdnf表达的变化;然而，很难检测到脑源性信号的菌株使用BLI与d-β-半乳糖苷酶，可能是因为不完整的底物分布和光穿透。我们证明，TokeOni，它均匀地分布在整个小鼠全身系统注射后，并产生近红外生物发光光，是适合于检测信号从脑的bdnf-Lucmouse。我们清楚地检测到在腹膜内注射TokeOni后穿过皮肤和颅骨的脑源性生物发光信号。然而，应限制使用TokeOni的重复BLI，因为在同一天重复注射TokeOni降低了生物发光信号，推测是通过产物抑制。我们成功地观察了海人酸诱导的海马中Bdnf的表达和感觉刺激诱导的视皮层中Bdnf的表达。总之，使用Bdnf-Lucmice和TokeOni的非侵入性近红外BLI使我们能够评估活体小鼠大脑中BDNF水平的变化。这将有助于更好地了解BDNF表达在神经系统疾病的发病机制和病理生理中的作用。
Altered levels of brain-derived neurotrophic factor (BDNF) have been reported in neurologically diseased human brains. Therefore, it is important to understand how the expression of BDNF is controlled under pathophysiological as well as physiological conditions. Here, we report a method to visualize changes in BDNF expression in the living mouse brain using bioluminescence imaging (BLI). We previously generated a novel transgenic mouse strain,Bdnf-Luciferase(Luc), to monitor changes inBdnfexpression; however, it was difficult to detect brain-derived signals in the strain using BLI withd-luciferin, probably because of incomplete substrate distribution and light penetration. We demonstrate that TokeOni, which uniformly distributes throughout the whole mouse body after systematic injection and produces a near-infrared bioluminescence light, was suitable for detecting signals from the brain of theBdnf-Lucmouse. We clearly detected brain-derived bioluminescence signals that crossed the skin and skull after intraperitoneal injection of TokeOni. However, repeated BLI using TokeOni should be limited, because repeated injection of TokeOni on the same day reduced the bioluminescence signal, presumably by product inhibition. We successfully visualized kainic acid-inducedBdnfexpression in the hippocampus and sensory stimulation-inducedBdnfexpression in the visual cortex. Taken together, non-invasive near-infrared BLI usingBdnf-Lucmice with TokeOni allowed us to evaluate alterations in BDNF levels in the living mouse brain. This will enable better understanding of the involvement of BDNF expression in the pathogenesis and pathophysiology of neurological diseases.