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  4. Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway

Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway

Acta Biochim Biophys Sin, 2023 · DOI: 10.3724/abbs.2023238 · Published: October 9, 2023

NeurologyGenetics

Simple Explanation

Electrical stimulation (ES) is used to treat central nervous system disorders. Researchers are studying how ES affects neurons and neural networks, depending on stimulation parameters. The mechanism of action of ES is still unclear. This study assesses changes in neurite number and axon length using immunofluorescence staining and Sholl analysis to determine the best ES pattern and parameters for neurons. Neuronal death and plasticity are also examined. Alternating current stimulation (ACS) has more significant effects on neurons than direct current stimulation (DCS). The PI3K/AKT pathway is crucial in how ACS affects neurons.

Study Duration
7 days
Participants
Primary cortical neurons from embryonic day 16‒18 Wistar rat embryos
Evidence Level
In vitro study

Key Findings

  • 1
    ACS at 3 μA for 20 min significantly increases the number of neurites, axon length, and spontaneous electrical activity of neurons.
  • 2
    ACS significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in neurotrophic factors.
  • 3
    PI3K/AKT-specific inhibitors abolish the beneficial effects of ACS on neurons, confirming the PI3K/AKT pathway's importance in the action of ACS.

Research Summary

This study investigates the effects of microcurrent electrical stimulation (direct/alternating current stimulation, DCS/ACS) on the behavior of primary cortical neurons using a conducting surface based on indium tin oxide (ITO) glass. The study found that ACS extensively changes neuronal transcription profiles, particularly in synapse plasticity, which is related to refined network neuronal circuit reform. The research identified that these changes may be attributed to an increase in GAP43 expression through the PI3K/AKT pathway, which plays an important role in axon branching and sprouting.

Practical Implications

Therapeutic Potential

The findings advance our understanding of the mechanisms underlying the therapeutic effects of ES, such as DBS and SCS.

Optimized Stimulation Parameters

The identification of optimal stimulation parameters (3 μA and 20 min for ACS) provides a basis for future applications.

Targeted Pathway Intervention

The confirmed involvement of the PI3K/AKT pathway suggests potential targets for enhancing the effects of electrical stimulation in neural regeneration.

Study Limitations

  • 1
    In vitro study
  • 2
    Specific parameters tested
  • 3
    Limited to cortical neurons

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