Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared biolumine
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RESEARCH
Open Access
Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared bioluminescence imaging Mamoru Fukuchi1* , Ryohei Saito2,3, Shojiro Maki2, Nami Hagiwara1, Yumena Nakajima1, Satoru Mitazaki1, Hironori Izumi4 and Hisashi Mori4
Abstract 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, BdnfLuciferase (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. Keywords: Bioluminescence, Brain-derived neurotrophic factor, In vivo imaging, Near-infrared
Introduction Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is fundamentally involved in a variety of functions in the developing and mature brain [1]. Consistent with the crucial roles of BDNF in the * Correspondence: [email protected] 1 Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan Full list of author information is available at the end of the article
central nervous system (CNS), alterations in BDNF levels have been found in the brains of patients with neurodegenerative or neuropsychiatric diseases [2–4]. Abnormal expression levels of BDNF have been reported in the postmortem brains of Alzheimer’s disease [5], Parkinson’s disease [6], Huntington’s disease [7], depression [8], and schizophrenia [9]. Higher expression levels of BDNF in the brain (dorsolateral prefrontal cortex) correlate with slower cognitive decline [10
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