Abstract
Brain-derived neurotrophic factor (BDNF) plays a fundamental role in expressing various neural functions including memory consolidation. Alterations of BDNF levels in the brain are associated with neurodegenerative and neuropsychiatric disorders. Therefore, it is important to understand how levels of BDNF are controlled. Recently we generated a novel transgenic mouse strain, termed the Bdnf-Luciferase transgenic (Bdnf-Luc Tg) mouse, to monitor changes in Bdnf expression. In the present study, we detected the bioluminescence signal from living Bdnf-Luc Tg mice after intraperitoneal administration of d-luciferin. Despite high levels of Bdnf expression in the brain, it was difficult to detect a signal from the brain region, probably because of its poorly penetrable (short-wavelength) bioluminescence. However, we could detect the changes in the bioluminescence signal in the brain region using a luciferin analogue generating a near-infrared wavelength of bioluminescence. We also found a strong correlation between increases in body weight and bioluminescence signal in the abdominal region of Tg mice fed a high-fat diet. These results show that changes in Bdnf expression can be visualized using living mice, and that the Tg mouse could be a powerful tool for clarification of the role of Bdnf expression in pathophysiological and physiological conditions.
Highlights
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and contributes to expression of a variety of neural functions, such as neuronal survival, differentiation, plasticity, learning, and memory[1,2,3,4]
We previously reported that intracerebroventricular injection of pituitary adenylate cyclase-activating polypeptide (PACAP), which is a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family and participates in a variety of neural functions[19], significantly increased the levels of Bdnf mRNA in the cerebral cortex of mice[16]
We showed that the changes in expression could be monitored by in vivo bioluminescence imaging with Bdnf-Luc Tg mice
Summary
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and contributes to expression of a variety of neural functions, such as neuronal survival, differentiation, plasticity, learning, and memory[1,2,3,4]. The regulation of human BDNF expression was investigated by enhanced-GFP (EGFP)-based in vivo analysis using the bacterial artificial chromosome (BAC) or the yeast artificial chromosome (YAC) clone containing human BDNF12, 13. In these reports, the expression of BDNF in brain sections prepared from transgenic mice was examined, and the results failed to demonstrate that changes in BDNF levels could be visualized in living mice. Our present study shows that the Bdnf-Luc Tg mouse would be a valuable tool for understanding changes in Bdnf levels under pathophysiological as well as physiological conditions and the role of Bdnf expression in living animals
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