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Toxicology in vitro : an international journal published in association with BIBRA2000; 14(5); 459-465; doi: 10.1016/s0887-2333(00)00037-0

Investigation of the susceptibility of equine autonomic neuronal cell lines, clonally derived from the same paravertebral ganglion, to toxic plasma from equine dysautonomia (grass sickness) cases.

Abstract: In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some neurones show abnormal changes while neighbouring neurones are unaffected. To test whether noradrenergic neurones showed variable susceptibility to the GS toxin in culture, clonally-derived populations isolated from the same fetal thoracic sympathetic chain ganglion were challenged with plasma from GS cases previously shown to induce ANS damage when injected into normal horses. During the early stages of exposure to toxic plasma, cells within a clonal population showed variable susceptibility ranging from no obvious effect to characteristic patterns of pathology. However, after 3 days of exposure to toxic plasma all cells were killed. Dose response analysis on selected clonal populations showed no significant difference in TD(50) values.
Publication Date: 2000-08-30 PubMed ID: 10963962DOI: 10.1016/s0887-2333(00)00037-0Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates the varying susceptibility of certain horse autonomic nervous system neurons, derived from the same ganglion, to a toxic substance found in cases of equine grass sickness. The study advocates that despite originating from the same source, these neurons displayed varied reactions when exposed to the toxin, ultimately leading to their demise.

Autonomic Nervous System and Grass Sickness

  • The research focuses on the reactions within the autonomic nervous system (ANS) of horses afflicted with grass sickness (GS), a debilitating condition with currently unknown cause(s).
  • This study uses as its basis, observations from affected horses where some neurons displayed abnormal changes whereas adjacent neurons remained unaffected.
  • The examination zeroes in on noradrenergic neurons due to their varied susceptibility to the GS toxin when studied in culture.

Study & Findings

  • The researchers utilised clonally-derived populations (cells cloned from a single parent cell, thus being genetically identical) which were isolated from the same fetal thoracic sympathetic chain ganglion – a group of nerve cells located near the spinal cord.
  • These cloned populations were then exposed to plasma (the straw-coloured liquid component of blood) from equine sufferers of GS. It was previously determined that this plasma has been shown to induce ANS damage when injected into healthy horses.
  • The report states that varying degrees of susceptibility were noticed within the cloned cell population. This ranged from insignificant impact to distinct patterns of pathological changes.
  • However, the study revealed that prolonged exposure to the toxic plasma resulted in the death of all tested cells after three days.

Dose-Response Analysis

  • A dose-response analysis was conducted on selected clonal populations. This process involves assessing the proportionate change in an outcome (in this case, neuron damage/death) with varying levels of exposure to the toxin.
  • This analysis found no significant discrepancy in TD(50) values. In pharmacology, TD(50) refers to the dose of a toxin at which 50% of the population is theoretically negatively impacted.
  • Despite cells originating from the same ganglion (and thus, expected to have similar genetic ability to resist the toxic impact), they did not show any significant difference in their ability to withstand GS plasma toxins.

Cite This Article

APA
John HA, Marrs J, Laffling AJ. (2000). Investigation of the susceptibility of equine autonomic neuronal cell lines, clonally derived from the same paravertebral ganglion, to toxic plasma from equine dysautonomia (grass sickness) cases. Toxicol In Vitro, 14(5), 459-465. https://doi.org/10.1016/s0887-2333(00)00037-0

Publication

ISSN: 0887-2333
NlmUniqueID: 8712158
Country: England
Language: English
Volume: 14
Issue: 5
Pages: 459-465

Researcher Affiliations

John, H A
  • Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, Scotland, UK. Johnh@mri.sari.ac.uk
Marrs, J
    Laffling, A J

      MeSH Terms

      • Animals
      • Antigens, Polyomavirus Transforming / metabolism
      • Autonomic Nervous System / metabolism
      • Autonomic Nervous System / pathology
      • Autonomic Nervous System Diseases / blood
      • Autonomic Nervous System Diseases / veterinary
      • Cell Line
      • Clone Cells
      • Dopamine beta-Hydroxylase / metabolism
      • Fluorescent Antibody Technique, Indirect
      • Ganglia, Sympathetic / metabolism
      • Ganglia, Sympathetic / pathology
      • Glial Fibrillary Acidic Protein / metabolism
      • Horse Diseases / blood
      • Horses
      • Neurons / metabolism
      • Neurons / pathology
      • Neuropeptide Y / metabolism
      • Plasma / physiology
      • Thorax / innervation

      Citations

      This article has been cited 2 times.
      1. Malekinejad H, Alizadeh-Tabrizi N, Ostadi A, Fink-Gremmels J. The role of sera from equine grass sickness on apoptosis induction in PC12 Tet-off p53 cell line.. Vet Res Forum 2015 Winter;6(1):9-15.
        pubmed: 25992246
      2. Edwards SE, Martz KE, Rogge A, Heinrich M. Edaphic and Phytochemical Factors as Predictors of Equine Grass Sickness Cases in the UK.. Front Pharmacol 2010;1:122.
        doi: 10.3389/fphar.2010.00122pubmed: 21833167google scholar: lookup