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 in Bdnf expression; however, it was difficult to detect brain-derived signals in the strain using BLI with d-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 the Bdnf-Luc mouse. 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-induced Bdnf expression in the hippocampus and sensory stimulation-induced Bdnf expression in the visual cortex. Taken together, non-invasive near-infrared BLI using Bdnf-Luc mice 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.

中文翻译：

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使用非侵入式近红外生物发光成像技术，观察活小鼠大脑中活性调节的BDNF表达。

据报道，在神经系统疾病的人脑中，脑源性神经营养因子（BDNF）的水平发生了变化。因此，重要的是要了解在病理生理以及生理条件下如何控制BDNF的表达。在这里，我们报告一种方法，使用生物发光成像（BLI）可视化活小鼠大脑中BDNF表达的变化。我们先前产生了一种新型的转基因小鼠品系Bdnf-荧光素酶（Luc），以监测Bdnf表达的变化。但是，使用BLI和d-萤光素来检测菌株中的脑源性信号很困难，这可能是因为底物分布不完全和光穿透性差。我们证明TokeOni在系统注射后均匀分布在整个小鼠体内，并产生近红外生物发光光，适用于检测来自Bdnf-Luc小鼠大脑的信号。我们清楚地检测到腹膜内注射TokeOni后穿过皮肤和头骨的脑源性生物发光信号。但是，应该限制使用TokeOni的重复BLI，因为在同一天重复注射TokeOni会降低生物发光信号，大概是由于产物抑制。我们成功地可视化海藻酸诱导的海马Bdnf表达和视觉皮层感觉刺激的Bdnf表达。两者合计，使用Bdnf-Luc小鼠和TokeOni的非侵入性近红外BLI，使我们能够评估活小鼠大脑中BDNF水平的变化。这将使人们能够更好地了解BDNF表达在神经系统疾病的发病机理和病理生理中的作用。