Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury

iScience, 2021 · DOI: 10.1016/j.isci.2021.102074 · Published: February 19, 2021

Simple Explanation

This study investigates using a gene called Neurod4 to help the spinal cord heal after an injury. Neurod4 is a transcription factor that promotes neuroregeneration after spinal cord injury (SCI) in mammals. The researchers used a special virus to deliver Neurod4 to stem cells in the spinal cord. This virus preferentially introduced Neurod4 into activated NSCs, which converted to neurons with axonal regrowth and suppressed the scar-forming glial lineage. The results showed that Neurod4 helped turn these stem cells into new neurons that could form connections and improve recovery after spinal cord injury. Thus, Neurod4 is a potential therapeutic factor that can improve anatomical and functional recovery after SCI.

Study Duration

6 weeks

Participants

9- to 10-week-old female and male C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Neurod4 promotes the conversion of ependymal cells to neural stem cells (NSCs) after spinal cord injury.
2
Neurod4 expression in activated NSCs leads to the differentiation of these cells into both excitatory and inhibitory neurons.
3
Neurod4-induced neurons form functional synapses with motor neurons, contributing to functional recovery after SCI.

Research Summary

The study identifies Neurod4 as a promising transcription factor for promoting neuroregeneration after spinal cord injury (SCI). Delivery of Neurod4 via a pseudotyped retroviral vector converts endogenous neural stem cells (NSCs) into neurons with axonal regrowth and suppressed glial scar formation. Neurod4-induced neurons form functional synapses and improve anatomical and functional recovery after SCI, suggesting its potential as a therapeutic factor.

Practical Implications

Therapeutic Potential

Neurod4 could be a potential therapeutic target for SCI.

Targeted Delivery

The LCMV-based retroviral vector provides a method for targeted gene delivery to neural stem cells.

Functional Recovery

Synaptic formation by Neurod4-induced neurons offers a pathway for functional recovery after SCI.

Study Limitations

1
The study is limited to a mouse model; neural circuits differ between primates and rodents.
2
Further experiments are needed to confirm the safety and efficacy of using a retroviral vector.
3
Electrophysiological confirmation of an efficient neural circuit after recovery from injury is needed.

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