Low-Intensity Focused Ultrasound Enhances Hippocampal Neurogenesis via BDNF Pathways: Toward a Regenerative Modality...

Area of Science:

• Neuroscience
• Biomedical Engineering
• Cell Biology

Background:

• Adult hippocampal neurogenesis is crucial for cognitive functions like learning and memory.
• The precise mechanisms by which physical stimuli modulate neurogenesis are not fully understood.
• Transcranial focused ultrasound is an emerging tool for non-invasive brain stimulation.

Purpose of the Study:

• To investigate the frequency-dependent effects of low-intensity focused ultrasound (LIFU) on adult hippocampal neurogenesis.
• To determine if LIFU modulates key neurogenic regulators and cognitive performance.
• To explore the role of ultrasound frequency in mechanotransduction-based brain plasticity.

Main Methods:

• Adult rats were subjected to LIFU targeting the dentate gyrus at different frequencies (0.5, 1, 5 MHz) twice weekly for 4 weeks.
• Cellular proliferation (BrdU incorporation) and neuronal differentiation (BrdU/NeuN co-labeling) were assessed.
• Hippocampal gene expression of neurogenic factors (BDNF, FGF-2, Sox-2) was quantified via qRT-PCR.
• Cognitive function was evaluated using the novel object recognition task.

Main Results:

• Low-frequency (0.5 MHz) LIFU significantly increased cell proliferation and neurogenesis markers in the dentate gyrus compared to sham controls.
• The 0.5 MHz frequency elevated hippocampal expression of BDNF, FGF-2, and Sox-2 mRNA.
• Improved recognition memory was observed exclusively in the 0.5 MHz stimulation group.
• Higher frequencies (1 and 5 MHz) yielded less pronounced effects on neurogenesis and cognition.

Conclusions:

• Ultrasound frequency critically influences the modulation of adult hippocampal neurogenesis and cognitive function.
• Low-frequency LIFU promotes neurogenesis and enhances memory, suggesting a mechanotransduction-dependent mechanism.
• These findings provide a basis for optimizing ultrasound parameters for therapeutic applications targeting brain plasticity and cognition.