Ascorbic Acid Promotes Functional Restoration after Spinal Cord Injury Partly by Epigenetic Modulation

Cells, 2020 · DOI: 10.3390/cells9051310 · Published: May 25, 2020

Spinal Cord Injury Genetics Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injuries are difficult to heal, and there are currently no effective treatments. This study investigated whether ascorbic acid (Vitamin C) can improve recovery after spinal cord injury by influencing DNA methylation, a process that can control gene expression. The researchers found that after a spinal cord injury in rats, the levels of a modified form of DNA called 5-hydroxymethylcytosine (5hmC) increased in the brain. They also observed an increase in the activity of genes called Tet genes, which are involved in DNA modification. Administering ascorbic acid to the rats after spinal cord injury further increased 5hmC levels, boosted Tet gene expression, promoted the growth of nerve fibers in the injured spinal cord, and improved the rats' ability to move.

Study Duration

3 months

Participants

Adult female Sprague-Dawley rats (12 weeks old, weighing 230–250 g)

Evidence Level

Not specified

Key Findings

1
SCI induces alteration of 5mC and 5hmC Levels in the Brain Motor Cortex. The intensity of 5hmC was signiﬁcantly higher in the SCI group than in the control group at 1 day (acute stage) and 1 week after injury.
2
AA Improves Functional Recovery and Axonal Sprouting after SCI. The ladder test revealed a greater restoration of hind limb function in the AA-100 group than in the control group at 2 weeks
3
AA Enhances 5hmC Formation by Upregulating Tet1 and Tet2. The average intensity of 5hmC was signiﬁcantly higher in the AA-100 group than in the control group at 1 week and 3 months

Research Summary

This study aimed to examine changes in neuronal DNA methylation status after SCI and to determine whether modulation of DNA methylation with ascorbic acid can enhance neuronal regeneration or functional restoration after SCI. The 5hmC level within the brain was increased after SCI, especially in the acute and subacute stages, and the mRNA levels of Tet gene family members (Tet1, Tet2, and Tet3) were also increased. In conclusion, we found that epigenetic status in the brain motor cortex is changed after SCI and that epigenetic modulation using ascorbic acid may contribute to functional recovery after SCI.

Practical Implications

Therapeutic Potential

Ascorbic acid may serve as a therapeutic agent to promote functional recovery after spinal cord injury.

Epigenetic Modulation

Epigenetic modulation through ascorbic acid may represent a novel approach to treating spinal cord injuries.

Further Research

Further studies are needed to understand the long-term effects and mechanisms of action of ascorbic acid in SCI recovery.

Study Limitations

1
The relationships between DNA demethylation and activation of some RAGs induced by AA application are not clear in this study.
2
The antioxidant eﬀects of AA might also attenuate the inﬂammatory response and concomitantly reduce lesion cavity size
3
Another limitation of this study was that the number of samples used for some analyses was small, while variations between samples were large

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