Trehalose enhances macrophage autophagy to promote myelin debris clearance after spinal cord injury

Cell & Bioscience, 2025 · DOI: https://doi.org/10.1186/s13578-025-01357-2 · Published: January 23, 2025

Simple Explanation

Spinal cord injury (SCI) often leads to a buildup of myelin debris, which impairs recovery. This study explores how trehalose, a natural sugar, can help macrophages clear this debris. Trehalose was found to boost autophagy in macrophages, helping them process and remove myelin debris more effectively. This reduces inflammation and promotes healing after SCI. By enhancing myelin clearance and reducing inflammation, trehalose supports nerve cell survival, axon regeneration, and motor function recovery, suggesting it as a potential SCI treatment.

Study Duration

28 days

Participants

C57BL/6 female mice (weight 20–25 g)

Evidence Level

Not specified

Key Findings

1
Trehalose enhances macrophage phagocytosis and clearance of myelin debris in a dose-dependent manner in vitro, with an optimal concentration of 20 mM.
2
In vivo, trehalose administration reduces myelin debris accumulation, inhibits foamy macrophage formation, suppresses inflammatory responses, and decreases fibrotic scarring after SCI.
3
Trehalose's beneficial effects are related to the overexpression of transcription factor EB (TFEB), a key regulator of the autophagy-lysosomal system.

Research Summary

This study demonstrates that trehalose enhances myelin debris clearance and reduces foamy macrophage formation after SCI by inducing TFEB expression in macrophages and modulating the autophagy-lysosomal system. By mitigating secondary inflammatory responses, trehalose decreased fibrotic scar and injury area sizes, thereby promoting axonal preservation and motor function recovery. These findings suggest that trehalose may represent a novel therapeutic approach for SCI.

Practical Implications

Therapeutic Potential

Trehalose may represent a novel therapeutic approach for spinal cord injury by enhancing myelin debris clearance and reducing foamy macrophage formation.

Clinical Application

Trehalose, being a safe and non-toxic natural sugar, has greater potential for clinical application due to its relatively inexpensive nature and ease of administration.

Inflammation Reduction

Trehalose can effectively reduce inflammatory responses, promote neuron survival, axonal preservation, and motor function recovery, making it a promising candidate for SCI treatment.

Study Limitations

1
The study primarily used female mice to avoid urinary complications; the role of sex in both pathology and treatment requires further investigation.
2
The specific mechanisms by which trehalose enhances TFEB overexpression post-spinal cord injury remain to be explored.
3
The study did not perform in vivo rescue experiments to provide more direct evidence for the restoration of autophagy-promoting functions regulated by trehalose.

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