Nkx6.1 enhances neural stem cell activation and attenuates glial scar formation and neuroinflammation in the adult injured spinal cord

Exp Neurol., 2021 · DOI: 10.1016/j.expneurol.2021.113826 · Published: November 1, 2021

Simple Explanation

This study explores the role of Nkx6.1, a gene important in spinal cord development, in adult spinal cord injury (SCI). The researchers used a lentivirus to deliver Nkx6.1 to the injured spinal cords of mice. They found that Nkx6.1 promoted the activation and proliferation of neural stem cells in the acute phase of SCI. In the chronic phase, Nkx6.1 reduced glial scar formation and neuroinflammation, while increasing the number of interneurons. The research suggests that Nkx6.1 has the potential to aid neural regeneration in the adult injured spinal cord by manipulating neural stem cells for damage repair and neuronal regeneration.

Study Duration

56 DPI

Participants

Young adult C57BL/6 mice (8–12 weeks-old)

Evidence Level

Not specified

Key Findings

1
Nkx6.1 expression increases NSPC activation and proliferation in the acute phase of SCI.
2
In the chronic phase of SCI, Nkx6.1 expression increases the number of cholinergic interneurons and reduces neuroinflammation and glial scar formation.
3
Transcriptomic analysis reveals that Nkx6.1 expression correlates with upregulation of genes involved in NSPC activation and axon guidance, and downregulation of genes associated with neuroinflammation and reactive astrocytes.

Research Summary

This study demonstrates that lentivirus-mediated Nkx6.1 expression promotes cell proliferation and activation of endogenous NSPCs, which correlates with a transient upregulation of the Notch signaling in the acute phase of injury. Nkx6.1 expression attenuates neuroinflammation and glial scar formation, which correlates with changes of gene expression involved in microglia and reactive astrocytes. The research suggests a potential application of Nkx6.1 expression for anti-inflammation management and manipulation of the glial scar and interneuron generation in the treatment of SCI.

Practical Implications

Therapeutic Potential

Nkx6.1 could be a potential therapeutic target for promoting neural regeneration after spinal cord injury.

NSPC Manipulation

Nkx6.1 may be useful for manipulating neural stem/progenitor cells (NSPCs) to promote neurogenesis and reduce glial scarring.

Anti-Inflammatory Strategy

Nkx6.1 expression may serve as an anti-inflammatory strategy in treating spinal cord injuries.

Study Limitations

1
Significant improvement in locomotor function was not observed
2
It is not clear whether the increased number of cholinergic interneurons were generated from NSPCs.
3
The molecular mechanisms underlying Nkx6.1 function in the adult remain elusive

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury