MCT1-mediated endothelial cell lactate shuttle as a target for promoting axon regeneration after spinal cord injury

Theranostics, 2024 · DOI: 10.7150/thno.96374 · Published: September 3, 2024

Simple Explanation

Spinal cord injuries disrupt the vascular system, leading to reduced oxygen and metabolic imbalances at the injury site. This study investigates how these metabolic changes affect the regeneration of nerve tissue and functional recovery. The study found that a protein called MCT1, which helps transport lactate (an energy source) from endothelial cells to neurons, is reduced after spinal cord injury. This reduction disrupts energy supply to neurons and hinders axon regeneration. By using a virus to restore MCT1 expression in endothelial cells, the researchers were able to enhance axon regeneration and improve functional recovery in mice with spinal cord injuries, suggesting a new therapeutic target.

Study Duration

Not specified

Participants

Adult male or female C57BL/6 mice (8-10 weeks old)

Evidence Level

Not specified

Key Findings

1
MCT1 expression is markedly decreased in endothelial cells (ECs) post-SCI, disrupting lactate transport to neurons.
2
Restoring MCT1 expression in ECs via adeno-associated virus enhances axonal regeneration and improves functional recovery in SCI mice.
3
Neurons utilize lactate to increase their glycolytic capacity, thereby promoting axon regeneration, which is enhanced by the MCT1-mediated lactate shuttle in ECs through direct contact.

Research Summary

This study highlights a novel metabolic pathway involving MCT1-mediated lactate shuttling from endothelial cells to neurons, which is crucial for energy metabolism and axon regeneration after spinal cord injury (SCI). The findings reveal that SCI-induced vascular damage leads to decreased MCT1 expression in endothelial cells, disrupting lactate transport to neurons, resulting in a metabolic imbalance that impedes axonal regeneration. Restoring MCT1 expression in endothelial cells enhances axonal regeneration and improves functional recovery in SCI mice, suggesting a new therapeutic target for SCI treatment.

Practical Implications

Therapeutic Target for SCI

MCT1 serves as a novel therapeutic target for SCI, providing a new direction after SCI treatment from a metabolic perspective.

Enhancing Neuronal Glycolysis

Targeting lactate transport mechanisms could promote axonal regeneration and neurological function recovery after SCI by enhancing neuronal glycolysis.

Maintaining Endothelial Lactate Homeostasis

Strategies should aim to shuttle lactate from endothelial cells to neurons, facilitating axonal regeneration and maintaining endothelial lactate homeostasis.

Study Limitations

1
The specific MCT members responsible for lactate uptake in neurons, their efficiency in lactate uptake, and their specific functions in vivo still require further investigation.
2
Whether other cells transport lactate to neurons after SCI, besides ECs, other cells may also contribute.
3
Whether vascular morphological changes and the loss of key proteins adversely affect recovery after SCI remains a subject for further investigation.

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