Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny

Mol Neurobiol, 2020 · DOI: 10.1007/s12035-019-01812-5 · Published: April 1, 2020

Simple Explanation

This study investigates whether folate supplementation in parent rodents can enhance spinal cord axon regeneration in their offspring, even without the offspring receiving folate directly. The research shows that enhanced axonal regeneration is observed in multiple generations of progeny, suggesting a transgenerational effect. This effect is linked to changes in DNA methylation and RNA transcription patterns, indicating a non-Mendelian inheritance mechanism.

Study Duration

Not specified

Participants

Sprague-Dawley Outbred rats, ICR Outbred mice, Fisher 344 inbred rats

Evidence Level

Not specified

Key Findings

1
Folate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1-F4) in the absence of interval folate administration to the progeny.
2
Transmission of the enhanced regeneration phenotype to progeny together with differential patterns of DNA methylation and RNA expression is consistent with a non-Mendelian mechanism.
3
Observation of folate-induced, transgenerational axon regeneration in both inbred and outbred rat lineages renders an artifact of breeding unlikely.

Research Summary

The study demonstrates that folate supplementation in parental rodents enhances spinal cord axon regeneration in multiple generations of their offspring, even without direct folate administration to the progeny. This transgenerational effect is associated with altered DNA methylation and RNA transcription patterns, suggesting a non-Mendelian inheritance mechanism. The findings have broad implications for the diagnosis, prevention, and treatment of inborn and acquired disorders, highlighting the potential of nutritional interventions to induce beneficial transgenerational phenotypes.

Practical Implications

Therapeutic Potential

Folate supplementation may offer a novel approach to enhance tissue healing and repair, particularly in the central nervous system.

Preventive Strategies

Understanding transgenerational effects can inform dietary and lifestyle choices to promote health across generations.

Personalized Medicine

Insights into epigenetic mechanisms may lead to tailored therapies for inherited and acquired conditions.

Study Limitations

1
A correlation observed between DNA methylation and the transgenerational axon regeneration phenotype does not preclude mechanisms of heritable transmission other than or in addition to DNA methylation
2
DNA sequence variations may directly or indirectly affect other methylation pathways
3
The gender of inheritance of the phenotype, and the critical interval during gestation most sensitive to supplementation, await ascertainment

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