Research Article: Vitamin E deficiency and risk of equine motor neuron disease

Date Published: July 2, 2007

Publisher: BioMed Central

Author(s): Hussni O Mohammed, Thomas J Divers, Brian A Summers, Alexander de Lahunta.

http://doi.org/10.1186/1751-0147-49-17

Abstract

Equine motor neuron disease (EMND) is a spontaneous neurologic disorder of adult horses which results from the degeneration of motor neurons in the spinal cord and brain stem. Clinical manifestations, pathological findings, and epidemiologic attributes resemble those of human motor neuron disease (MND). As in MND the etiology of the disease is not known. We evaluated the predisposition role of vitamin E deficiency on the risk of EMND.

Eleven horses at risk of EMND were identified and enrolled in a field trial at different times. The horses were maintained on a diet deficient in vitamin E and monitored periodically for levels of antioxidants – α-tocopherols, vitamins A, C, β-carotene, glutathione peroxidase (GSH-Px), and erythrocytic superoxide dismutase (SOD1). In addition to the self-control another parallel control group was included. Survival analysis was used to assess the probability of developing EMND past a specific period of time.

There was large variability in the levels of vitamins A and C, β-carotene, GSH-Px, and SOD1. Plasma vitamin E levels dropped significantly over time. Ten horses developed EMND within 44 months of enrollment. The median time to develop EMND was 38.5 months. None of the controls developed EMND.

The study elucidated the role of vitamin E deficiency on the risk of EMND. Reproducing this disease in a natural animal model for the first time will enable us to carry out studies to test specific hypotheses regarding the mechanism by which the disease occurs.

Partial Text

Spontaneous motor neuron diseases are uncommon in domestic animals. Where they have been subject to study, these disorders invariably demonstrate a familial pattern, occurring in specific breeds of animals such as Brittany Spaniel dogs [1], Brown Swiss cattle [2] and Yorkshire pigs [3]. Clinical deficits are evident in the first year of life and often by a few months of age. The neuropathologic findings are a common theme of neurofilament accumulation in neurons and proximal axons, progressive motor neuron degeneration and spinal muscular atrophy. Accordingly, in 1990, considerable excitement accompanied the identification [4] of equine motor neuron disease (EMND), a sporadically occurring motor neuron disease affecting several horse breeds including standardbred, thoroughbred, Quarter horse and Arab breeds. The disorder presents in adult horses with a median age of 10 years. While EMND has been observed most frequently in the Quarter Horse breed, we believe that this is due to the manner in which these horses are housed and fed rather than by a primary genetic determination.

In the years after 1990, the newly identified EMND was viewed as sharing clinical and neuropathologic features with human MND [4,11] While on epidemiologic grounds, the equine disease appeared to be purely sporadic, we decided to examine equine SOD1 for polymorphisms given the association of mutations in this gene and familial human MND. No association between SOD1 variants and EMND were found [25]. In contrast, our field visits to farms with EMND cases suggested a connection between certain dietary practices and the disorder. We found cases of EMND commonly where horses had no access to pasture or other green feed and were fed poor quality food/hay [5,10,14]. Specifically, we performed this study to investigate a possible causal relation between a dietary deficiency of vitamin E and the risk of EMND. The previous evidence was built through observational studies and, by virtue of their nature, it is impossible to establish causal relationship between the deficiency in this antioxidant and the risk of EMND [26]. Vitamin E determinations on the EMND-afflicted cases and control horses in the prior observational studies were made at the time of disease diagnosis. At such a time in the course of this motor neuron disease, it is impossible to discern which took place first, the deficiency in the antioxidant or the development of the disease. Therefore, it was important to carry out this dietary trial to establish the chronological sequence of events and confirm the suspected causal relationship between the deficiency and the risk of the disease.

We believe that EMND, just as ALS, may have a multifactorial etiology and that oxidative stress is a major contributing/predisposing factor, i.e., sufficient cause, in motor neuron death but not necessarily the sole etiologic agent/factor. While the dietary practices which appear to favor the development of hypovitaminosis E in horses are not new, EMND was not identified prior to 1990. This would suggest that more than vitamin E deficiency is in play. By reproducing the disease, we are an in a position to test specific hypotheses regarding the etiologic factor(s) while taking into consideration the role of oxidative stress. Through these etiologic studies we will be able to understand the pathogeneses of the motor neuron disease and may be able to provide new therapeutic avenues either by amelioration of the etiologic agent(s) or enforcement of the oxidative defense.

HM conceived the study, developed the experimental design in collaboration with the authors, coordinated the different activities, performed the statistical analyses, and drafted the manuscript. TD participated in the development of the design, recruited the horses for the study, oversee the implementation of the field trial, and performed the clinical diagnosis; BS carried out the histopathological studies in collaboration with AD. AD performed the neurological diagnosis, carried out the postmortem studies and histopathological studies. All authors read and provide the final draft of the manuscript.

 

Source:

http://doi.org/10.1186/1751-0147-49-17

 

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