Bioelectric stimulation outperforms brain derived neurotrophic factor in promoting neuronal maturation

Area of Science:

• Neuroscience
• Biotechnology
• Cell Biology

Background:

• Neuronal differentiation and maturation are vital for research models and therapies.
• Biochemical stimuli like BDNF have limitations in broad cellular effects.
• Electrical stimulation (ES) offers physical control but lacks standardized protocols.

Purpose of the Study:

• To compare the efficacy of ES versus BDNF in promoting neuronal maturation.
• To identify key ES parameters regulating cellular responses in neuronal differentiation.
• To establish optimized ES protocols for in vitro neuronal culture.

Main Methods:

• Tested pulsed ES regimes on human neuroblastoma SH-SY5Y cells.
• Utilized electrochemical characterization and equivalent circuit modeling to determine ES parameters.
• Quantified neuronal maturation markers, including neurite outgrowth, synaptophysin expression, and extracellular vesicle (EV) cargo.

Main Results:

• ES significantly outperformed BDNF in promoting neuronal maturation and neurite outgrowth.
• Accumulated charge was identified as a key parameter, with higher levels (~50 mC/h) enhancing maturation and synaptophysin expression.
• Lower charge accumulation (~0.1 mC/h) promoted cell proliferation, while optimized ES enriched EV proteome for neural development.

Conclusions:

• Accumulated charge is a critical determinant of ES-induced cellular responses in neuronal differentiation.
• Optimized ES protocols can effectively induce complex neuronal morphologies and enhance neural function markers, surpassing BDNF.
• Controlled ES presents a promising, chemically minimal approach for generating mature neuronal cultures in vitro.