Gsx1 promotes locomotor functional recovery after spinal cord injury

Molecular Therapy, 2021 · DOI: https://doi.org/10.1016/j.ymthe.2021.04.027 · Published: August 1, 2021

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study explores a potential treatment for spinal cord injury (SCI) by promoting tissue regeneration using residential cells, specifically neural stem and progenitor cells (NSPCs). The challenge is that adult NSPCs often differentiate into glial cells, contributing to scar formation at the injury site. The researchers focused on Gsx1, a factor known to regulate the development of interneurons in the spinal cord. They found that increasing Gsx1 expression in mice with SCI led to an increase in NSPCs and the generation of specific types of interneurons. Importantly, Gsx1 reduced scar formation, enhanced serotonin neuronal activity, and improved locomotor function in the injured mice. This suggests Gsx1 gene therapy could be a promising approach for treating spinal cord injuries.

Study Duration

56 DPI

Participants

8- to 12-week-old mice

Evidence Level

Not specified

Key Findings

1
Gsx1 expression increases the number of NSPCs in a mouse model of lateral hemisection SCI during the acute stage.
2
Gsx1 expression increases the generation of glutamatergic and cholinergic interneurons and decreases the generation of GABAergic interneurons in the chronic stage of SCI.
3
Gsx1 reduces reactive astrogliosis and glial scar formation, promotes serotonin (5-HT) neuronal activity, and improves the locomotor function of the injured mice.

Research Summary

This study demonstrates that Gsx1 expression increases NSPCs and the generation of specific interneuron subtypes, including vGlut2+ and ChAT+ interneurons, and 5-HT neuronal activity, while reducing inhibitory GABAergic neurons. Gsx1 attenuates reactive astrogliosis and glial scar formation and promotes locomotor functional recovery in mice with SCI. The findings suggest Gsx1 gene therapy as a promising treatment for injuries to the spinal cord and perhaps other parts of the CNS.

Practical Implications

Therapeutic Potential

Gsx1 gene therapy could be a promising treatment for spinal cord injuries and other CNS injuries.

Interneuron Regeneration

Gsx1 promotes the generation of specific interneuron subtypes, which are crucial for transmitting motor and sensory impulses.

Scar Reduction

Gsx1 reduces glial scar formation, which is a major hurdle for neural regeneration and functional recovery after SCI.

Study Limitations

1
The study cannot rule out the possibility that Gsx1 can reprogram residential glial cells into neurons or promote survival of the neurons at the lesion site.
2
Future cell-lineage tracing experiments using a cell-speciﬁc promoter for targeted expression of Gsx1 in glial cells or NSPCs are needed to determine the origin of Gsx1-induced neurons.
3
The study used a mouse model of SCI, and the results may not be directly applicable to humans.

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