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Home / Equine Research Bank / BMC Vet Res / Restoring pars intermedia dopamine concentrations and tyrosi...
BMC veterinary research2020; 16(1); 356; doi: 10.1186/s12917-020-02565-3

Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction.

Abstract: Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses. To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively. Results: DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID. Conclusions: These findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases.
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Publication Date: 2020-09-25 PubMed ID: 32977825PubMed Central: PMC7517620DOI: 10.1186/s12917-020-02565-3Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores the effectiveness of pergolide treatment in restoring dopamine concentrations and tyrosine hydroxylase expression levels in horses with Pituitary Pars Intermedia Dysfunction (PPID), potentially offering insights for human neurodegenerative diseases.

Background

  • The authors of this research studied PPID, a condition that typically affects older horses.
  • PPID is characterized by the degeneration of hypothalamic dopaminergic neurons, which causes the proliferation of pars intermedia (PI) melanotropes due to hyperplasia and adenoma formation.
  • This results in considerably reduced dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity in PI tissue.
  • Previous observations have shown that treatment with pergolide, a dopamine receptor agonist, significantly improves the clinical condition of horses affected by PPID.

Hypothesis

  • Based on the above-observed clinical improvement, the authors hypothesized that treating PPID-affected horses with pergolide could result in higher dopamine and tyrosine hydroxylase levels, compared to untreated PPID-affected horses.

Experiment

  • To test their hypothesis, the researchers removed the pituitary glands from 18 horses, which included untreated and treated PPID-affected horses, as well as horses without signs of PPID.
  • The treated horses received a daily, oral dose of pergolide for 6 months.
  • DA concentrations and TH expression levels were then determined from the collected PI tissues, with the aid of high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively.

Results

  • The results demonstrated that DA and TH levels were lowest in the PI tissues collected from untreated horses with PPID.
  • In contrast, horses that were treated with pergolide showed DA and TH levels similar to those observed in aged horses without PPID symptoms.

Conclusion

  • These findings empirically support the initial hypothesis, showing that pergolide treatment can restore DA and TH levels in PPID-affected horses.
  • Furthermore, the authors suggest that equine PPID could serve as a potential animal model for studying human neurodegenerative disorders linked to dopaminergic neurodegeneration.

Cite This Article

APA
Fortin JS, Benskey MJ, Lookingland KJ, Patterson JS, Howey EB, Goudreau JL, Schott HC. (2020). Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction. BMC Vet Res, 16(1), 356. https://doi.org/10.1186/s12917-020-02565-3

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 16
Issue: 1
Pages: 356
PII: 356

Researcher Affiliations

Fortin, Jessica S
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, 48824, MI, USA. fortinj1@msu.edu.
Benskey, Matthew J
  • Department of Pharmacology and Toxicology, Neuroscience Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Lookingland, Keith J
  • Department of Pharmacology and Toxicology, Neuroscience Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Patterson, Jon S
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, 48824, MI, USA.
Howey, Erin B
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, 48824, MI, USA.
Goudreau, John L
  • Department of Pharmacology and Toxicology, Neuroscience Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
  • Neurology and Ophthalmology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
Schott, Harold C
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, 48824, USA. schott@msu.edu.

MeSH Terms

  • Aging
  • Animals
  • Dopamine / metabolism
  • Dopamine Agonists / therapeutic use
  • Horse Diseases / drug therapy
  • Horses
  • Pergolide / therapeutic use
  • Pituitary Diseases / drug therapy
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate / drug effects
  • Pituitary Gland, Intermediate / pathology
  • Tyrosine 3-Monooxygenase / metabolism

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
  1. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  2. Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott HC 2nd. Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy.. Sci Rep 2021 Aug 6;11(1):16036.
    doi: 10.1038/s41598-021-95396-7pubmed: 34362943google scholar: lookup
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