Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses

Abstract

BackgroundPhosphorylated neurofilament heavy, a marker of neuroaxonal damage, is increased in horses with equine neuroaxonal dystrophy. However, the temporal dynamics of this biomarker during the post‐natal risk period are not understood.ObjectiveTo measure serum and cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile foals across the post‐natal window of susceptibility for equine neuroaxonal dystrophy.Study designCase–control in vivo experimental study.MethodsConcentrations of phosphorylated neurofilament heavy were measured using frozen serum and cerebrospinal fluid collected from 13 foals raised in a vitamin E deficient environment from 1 to 6 months of age. Four of these foals were produced by equine neuroaxonal dystrophy‐affected dams, developed clinical signs consistent with equine neuroaxonal dystrophy and had a diagnosis confirmed by histopathology. The remaining nine foals, produced by healthy mares, were vitamin E depleted and remained clinically healthy. An additional cohort of foals, produced by healthy mares, were supplemented with vitamin E (α‐tocopherol; α‐TOH) from birth and sampled similarly.ResultsSerum α‐TOH concentrations were significantly higher in vitamin E supplemented healthy foals. Serum phosphorylated neurofilament heavy concentrations did not differ significantly between groups at any time point. Cerebrospinal fluid phosphorylated neurofilament heavy concentrations increased with age in healthy vitamin E depleted foals (p < 0.001); an effect that was not observed in healthy vitamin E supplemented foals.Main limitationsA genetically susceptible cohort supplemented with vitamin E was not available for comparison.ConclusionWe demonstrate that vitamin E depletion may elevate cerebrospinal fluid phosphorylated neurofilament heavy in otherwise healthy juvenile foals by 6 months of age. We highlight an important cofactor to consider when interpreting cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile horses.

Measurement of 8‐hydroxy‐2′‐deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia

“…9 Low vitamin E and limited access to pasture within the first year of life has been discussed in multiple studies as an underlying etiology. 3,9,16,18,19,21 When accounting for vitamin E concentration, no difference in 8-OHdG was identified. Without continued oxidative damage it could be that 8-OHdG would not be found in high concentrations in the CNS of horses with NAD/DM.…”

“…Providing access to green pastures in foals has been discussed as a potentially protective mechanism against EDM 9 . Low vitamin E and limited access to pasture within the first year of life has been discussed in multiple studies as an underlying etiology 3,9,16,18,19,21 . When accounting for vitamin E concentration, no difference in 8‐OHdG was identified.…”