Neuronal injury: folate to the rescue?

This commentary discusses a study by Iskandar and colleagues published in the same issue of the JCI, which investigates the role of folate in nerve regeneration after injury in rodents. The study shows that folate plays a crucial role in the regeneration of spinal neurons after injury, and that this regeneration depends on DNA methylation pathways. Folate, also known as vitamin B9, is important for single-carbon metabolism, particularly in generating methyl groups needed for cellular methylation. Folate deficiency can lead to DNA hypomethylation, affecting gene expression. The commentary also highlights that the brain is relatively protected from folate deficiency compared to other tissues, and that folate uptake across the blood-CSF barrier is facilitated by membrane-bound folate receptors.

• 1
  Iskandar et al. found that after injury to somatosensory axons in rodents, there was an increase in the expression of the α-isoform of folate receptor 1 (FOLR1).
• 2
  The SAM/SAH ratio, important for cellular methylation, declined after spinal cord injury. Folate supplementation increased regeneration of spinal neurons and retinal ganglion cells in wild-type animals.
• 3
  The therapeutic effect of folic acid had an inverted U-shaped relationship with the dose administered, with peak effects at 80 μg/kg. DNMT agonism promoted, and DNMT antagonism inhibited, growth of injured sensory spinal axons into the nerve graft.