Visualizing Changes in Brain-Derived Neurotrophic Factor Expression in Living Mice Using the All-Engineered...

Area of Science:

• Neuroscience
• Molecular Biology
• Biotechnology

Background:

• Brain-derived neurotrophic factor (BDNF) is crucial for neuronal health and cognitive function.
• Dysregulation of BDNF is linked to neurodegenerative and neuropsychiatric disorders.
• Noninvasive in vivo monitoring of BDNF expression is needed to study its role in brain function and disease.

Purpose of the Study:

• To develop a novel transgenic mouse model and bioluminescence imaging system for noninvasive, real-time monitoring of BDNF expression in vivo.
• To assess the utility of this system in tracking activity-dependent BDNF changes and in disease models.

Main Methods:

• Development of Bdnf-AkaLuc transgenic (Tg) mice by replacing the BDNF coding region with a mutant luciferase (AkaLuc).
• Utilized AkaBLI, a near-infrared bioluminescence imaging system optimized for deep-tissue detection.
• Validated the system in response to pilocarpine-induced status epilepticus and in a 5xFAD Alzheimer's disease mouse model.

Main Results:

• The AkaBLI system demonstrated robust and highly sensitive detection of bioluminescence in mouse brains, outperforming previous models.
• Successfully visualized activity-dependent BDNF mRNA induction during seizures.
• Enabled longitudinal monitoring through optimized imaging intervals and a hairless Tg line.
• Detected reduced BDNF expression in the brains of 5xFAD Alzheimer's disease model mice.

Conclusions:

• The Bdnf-AkaLuc Tg mice and AkaBLI system provide a powerful tool for noninvasive, continuous visualization of BDNF regulation.
• This approach facilitates the study of BDNF in physiological and pathological conditions.
• The imaging system holds potential for advancing understanding of BDNF-related brain function and for therapeutic strategy evaluation.