Blood and Cerebrospinal Fluid α‐Tocopherol and Selenium Concentrations in Neonatal Foals with Neuroaxonal Dystrophy

Abstract

BackgroundEquine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on α-tocopherol (α-TP)-deficient diet.ObjectiveIntramuscular α-TP and selenium (Se) administration at 4 days of age would have no significant effect on serum or cerebrospinal fluid (CSF) α-TP in healthy foals. Serum and CSF α-TP, but not Se, would be significantly decreased in NAD/EDM-affected foals during first year of life.AnimalsFourteen Quarter horse foals; 10 healthy foals supplemented with 0.02 mL/kg injectable α-TP and Se (n = 5) or saline (n = 5) at 4 days of age and 4 unsupplemented NAD/EDM-affected foals.MethodsComplete neurologic examinations were performed, blood and CSF were collected before (4 days of age) and after supplementation at 10, 30, 60, 120, 180, 240, and 360 days of age. Additional blood collections occurred at 90, 150, 210, and 300 days. At 540 days, NAD/EDM-affected foals and 1 unsupplemented healthy foal were euthanized and necropsies performed.ResultsSignificant decreases in blood, CSF α-TP and Se found in the first year of life in all foals, with most significant changes in serum α-TP from 4–150 days. Dam α-TP and Se significantly influenced blood concentrations in foals. Injection of α-TP and Se did not significantly increase CSF Se, blood or CSF α-TP in healthy foals. NAD/EDM-affected foals had significantly lower CSF α-TP through 120 days.Conclusions and Clinical ImportanceInjection of α-TP and Se at 4 days of age does not significantly increase blood or CSF α-TP. Despite all 14 foals remaining deficient in α-TP, only the 4 genetically predisposed foals developed NAD/EDM.

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes

“…Only these four genetically susceptible foals developed clinical and histologic evidence of eNAD. In these foals, significantly lower CSF α-TOH concentrations in eNAD foals, as compared to heathy foals maintained on the same α-TOH deficient diet, were found through 120 days of age (9). Based on the evidence that an α-TOH deficiency results in neurodegeneration in AVED and overlapping clinical and neuropathologic features of the α-TOH deficient phenotypes with AVED, Ttpa −/− mice and eNAD, there is likely a cause-and-effect role of α-TOH in eNAD.…”

“…1). While these concentrations reflect one time point, we have recently published a longitudinal study examining 14 foals maintained on a diet deficient in α-TOH from birth through 8 months of age (9). Ten of the foals in that study were out of healthy dams and sires and four were out of eNAD dams (i.e.…”

“…Unaffected horses were euthanized for reasons other than neurologic disease and a full neuropathologic evaluation was performed. Alpha-TOH concentrations were assessed as previously described (1, 9) and concentrations compared using a Mann-Whitney test with significance set at P <0.05.…”

“…In more severely affected horses, the disease is often termed equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) and histologic lesions include axonal loss and demyelination of specific neuroanatomic tracts within the cervicothoracic spinal cord (1). Equine NAD develops in genetically predisposed foals maintained on an α-tocopherol (α-TOH) deficient diet during the first year of life (3). Similar to AVED, the development of clinical signs can be prevented by early long-term α-TOH supplementation (1, 4).…”

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project

“…Immediately post-mortem , cerebrospinal fluid (CSF), synovial fluid and urine were collected. CSF was collected at the atlanto-occipital site, as previously described (Finno et al 2015). Synovial fluid was collected via syringe aspiration of the carpal and tarsal joints from ECA_UCD_AH1.…”