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Veterinary pathology2015; 53(1); 77-86; doi: 10.1177/0300985815598787

Evidence of the Primary Afferent Tracts Undergoing Neurodegeneration in Horses With Equine Degenerative Myeloencephalopathy Based on Calretinin Immunohistochemical Localization.

Abstract: Equine degenerative myeloencephalopathy (EDM) is characterized by a symmetric general proprioceptive ataxia in young horses, and is likely underdiagnosed for 2 reasons: first, clinical signs overlap those of cervical vertebral compressive myelopathy; second, histologic lesions--including axonal spheroids in specific tracts of the somatosensory and motor systems--may be subtle. The purpose of this study was (1) to utilize immunohistochemical (IHC) markers to trace axons in the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts in healthy horses and (2) to determine the IHC staining characteristics of the neurons and degenerated axons along the somatosensory tracts in EDM-affected horses. Examination of brain, spinal cord, and nerves was performed on 2 age-matched control horses, 3 EDM-affected horses, and 2 age-matched disease-control horses via IHC for calbindin, vesicular glutamate transporter 2, parvalbumin, calretinin, glutamic acid decarboxylase, and glial fibrillary acidic protein. Primary afferent axons of the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts were successfully traced with calretinin. Calretinin-positive cell bodies were identified in a subset of neurons in the dorsal root ganglia, suggesting that calretinin IHC could be used to trace axonal projections from these cell bodies. Calretinin-immunoreactive spheroids were present in EDM-affected horses within the nuclei cuneatus medialis, cuneatus lateralis, and thoracicus. Neurons within those nuclei were calretinin negative. Cell bodies of degenerated axons in EDM-affected horses are likely located in the dorsal root ganglia. These findings support the role of sensory axonal degeneration in the pathogenesis of EDM and provide a method to highlight tracts with axonal spheroids to aid in the diagnosis of this neurodegenerative disease.
Publication Date: 2015-08-07 PubMed ID: 26253880PubMed Central: PMC4831571DOI: 10.1177/0300985815598787Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper seeks to understand more about Equine Degenerative Myeloencephalopathy (EDM), a neurodegenerative disease in horses, focusing on the part of the nervous system known as the primary afferent tracts. The research provides evidence of neurodegeneration in these areas, particularly in dampening sensitivity pathways, as a contributing factor to EDM, revealed through the use of specific protein markers (calretinin).

Objectives of the Study

  • The primary aim of the study was to use immunohistochemical (IHC) markers to trace axons (nerve fibres) in healthy horse’s neurologic pathways, namely spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts.
  • The secondary objective was to identify the IHC staining characteristics of neurons and degenerated axons along the pathways associated with sensations in horses affected by EDM.

Experimental Procedure

  • This study involved exploring the brains, spinal cords, and nerves of two healthy control horses, three EDM-affected horses, and two other disease control horses.
  • IHC staining for various proteins, including calbindin, vesicular glutamate transporter 2, parvalbumin, calretinin, glutamic acid decarboxylase, and glial fibrillary acidic protein was done.
  • The primary afferent axons of three tracts were successfully traced using calretinin, a calcium-binding protein widely used as a marker for neurons and nerve fibres.

Study Results

  • In the dorsal root ganglia, a group of neurons in the spinal cord, researchers found calretinin-positive cell bodies. The findings suggest that calretinin IHC may be used to trace axonal projections from these cells.
  • Among the EDM-affected horses, calretinin-immunoreactive spheroids (markers of axonal damage) were observed within the nuclei cuneatus medialis, cuneatus lateralis, and thoracicus. However, neurons within these nuclei were lacking in calretinin.
  • It is likely that the cell bodies of degenerated axons in horses with EDM are located in the dorsal root ganglia.

Conclusion

  • The findings reaffirm the role of sensory axonal degeneration in the onset of EDM and suggest a new method to trace tracts with axonal spheroids, all of which could assist in diagnosing this disease.
  • The use of calretinin as an effective tool to visualize neurons and nerve fibres could be significant in the study and understanding of the disease as it highlights the specific pathways affected, making the disease easier to diagnose.

Cite This Article

APA
Finno CJ, Valberg SJ, Shivers J, D'Almeida E, Armién AG. (2015). Evidence of the Primary Afferent Tracts Undergoing Neurodegeneration in Horses With Equine Degenerative Myeloencephalopathy Based on Calretinin Immunohistochemical Localization. Vet Pathol, 53(1), 77-86. https://doi.org/10.1177/0300985815598787

Publication

ISSN: 1544-2217
NlmUniqueID: 0312020
Country: United States
Language: English
Volume: 53
Issue: 1
Pages: 77-86

Researcher Affiliations

Finno, C J
  • Department of Veterinary Population Medicine, University of Minnesota, St Paul, MN, USA cjfinno@ucdavis.edu.
Valberg, S J
  • Department of Veterinary Population Medicine, University of Minnesota, St Paul, MN, USA cjfinno@ucdavis.edu.
Shivers, J
  • Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA cjfinno@ucdavis.edu.
D'Almeida, E
  • Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA.
Armién, A G
  • Department of Veterinary Population Medicine, University of Minnesota, St Paul, MN, USA Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA.

MeSH Terms

  • Animals
  • Ataxia / pathology
  • Ataxia / veterinary
  • Brain Diseases / pathology
  • Brain Diseases / veterinary
  • Calbindins / metabolism
  • Horse Diseases / pathology
  • Horses
  • Immunohistochemistry / veterinary
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / veterinary
  • Neurons / pathology
  • Spinal Cord / pathology
  • Spinal Cord Diseases / pathology
  • Spinal Cord Diseases / veterinary

Grant Funding

  • K01 OD015134 / NIH HHS
  • L40 TR001136 / NCATS NIH HHS
  • 1K01OD015134-01A1 / NIH HHS

Conflict of Interest Statement

Declaration of Conflicting Interests. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Citations

This article has been cited 12 times.
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