Deletion of the Fractalkine Receptor, CX3CR1, Improves Endogenous Repair, Axon Sprouting, and Synaptogenesis after Spinal Cord Injury in Mice

The Journal of Neuroscience, 2017 · DOI: 10.1523/JNEUROSCI.2841-16.2017 · Published: March 29, 2017

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

This study investigates how removing a specific receptor, CX3CR1, affects recovery after spinal cord injury in mice. CX3CR1 is found on microglia and macrophages, immune cells in the spinal cord. The researchers found that mice lacking CX3CR1 showed improved spinal cord repair, including the growth of new nerve fibers and connections, especially in areas related to motor function. This suggests that targeting CX3CR1 could be a new approach to improve recovery after spinal cord injuries by reducing inflammation and promoting the nervous system's ability to adapt and repair itself.

Study Duration

56 d

Participants

104 male and female CX3CR1, or CX3CR1 mice

Evidence Level

Level 1, Animal Study

Key Findings

1
CX3CR1 deficiency in microglia and macrophages promotes a tissue-repair phenotype and increases expression of neurotrophic and gliogenic proteins after spinal cord injury.
2
Deletion of CX3CR1 enhances NG2 glial cell responses, axon sparing, and sprouting of serotonergic axons at the lesion epicenter.
3
In the lumbar spinal cord, CX3CR1 deletion is associated with enhanced axon and synaptic plasticity and reduced dendritic pathology on spinal motor neurons.

Research Summary

This study demonstrates that deleting CX3CR1, a chemokine receptor primarily found on microglia and a subset of macrophages, enhances neuroprotection and plasticity in spared fibers following spinal cord injury (SCI). The absence of CX3CR1 signaling leads to functional changes in microglia and macrophages, shifting them from a neurotoxic to a tissue-repair phenotype, characterized by increased expression of neurotrophic factors. These changes result in improved axon sparing, enhanced NG2 glial cell response, increased serotonergic axon sprouting at the injury site, and enhanced synaptic plasticity in lumbar spinal cord motor neurons, suggesting CX3CR1 as a potential therapeutic target for SCI.

Practical Implications

Therapeutic Target

CX3CR1 is a potential therapeutic target for enhancing neuroplasticity and recovery after spinal cord injury.

Reduce Adverse Effects

Interventions that specifically target CX3CR1 could reduce the adverse effects of intraspinal inflammation.

Augment Plasticity

Limiting CX3CR1-dependent signaling could improve rehabilitation and spinal learning.

Study Limitations

1
The study was performed on mice and may not directly translate to humans.
2
The specific molecular mechanisms controlling CX3CR1-dependent signaling require further investigation.
3
Whether manipulating CX3CR1 can augment structural and functional plasticity alone or as an adjunct to facilitate rehabilitation requires future studies.

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